/ en Tue, 14 Apr 26 09:00:00 -0400 /news/base-editing-repairs-mutation-and-liver-function-mouse-model-zellweger-spectrum-disorder <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" class="datetime">April 14, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The base editing enzyme used in this study is the same one that fixed Baby KJ Muldoon’s disease-causing mutation and saved his life in 2025.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" title="Tuesday, April 14, 2026 - 09:00" class="datetime">April 14, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A letter C is penciled into a long DNA sequence. "> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=x65fUlJp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=bcuAAMZD 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=WwHaTNVb 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy" alt="A letter C is penciled into a long DNA sequence. " title="A letter C is penciled into a long DNA sequence. " typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Susanna Hamilton </div> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/2196/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2196/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2196/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li data-list-item-id="e8d1325b084ac3c4798f4fe8846f1bfbc">Zellweger spectrum disorder is a group of genetic conditions that affect multiple organs in the body and the most severe form can be fatal in the first year of life.</li> <li aria-level="1" data-list-item-id="ee50c6be27935e16cc0c6f58877166496">Scientists used base editing to correct a disease-causing mutation in the <em>PEX1</em> gene in human cells and mice. This restored the function of peroxisomes, an organelle in the cell that malfunctions in these disorders.</li> <li aria-level="1" data-list-item-id="e345218bc482a038c22e0d62b5b42253a">The study, which began in 2020, guided the team to focus on a key base editor component — a deaminase enzyme — that was subsequently used to treat baby KJ Muldoon with a different genetic disease in 2025.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>In 2025, baby KJ Muldoon <a target="_blank" href="https://www.chop.edu/news/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital">became the first person</a> to receive a personalized gene editing treatment, which likely saved his life. But the scientific advances that made the groundbreaking treatment possible were years in the making long before KJ was born. One was base editing, the technology developed in 2016 by David Liu and his lab at the ӳ����ý that makes single-letter changes in DNA and was used to correct KJ’s life-threatening mutation.  </p> <p>Another advancement was the development and characterization of a specific version of a key base editor component: the enzyme called a deaminase, which converts a disease-causing DNA letter into a healthy one. Efforts to identify an optimal deaminase for a different genetic disorder began in 2020 in a collaboration between Liu’s lab and scientists from Jackson Laboratory and the University of Southern California (USC). The results of this project, published today in <a target="_blank" href="https://www.nature.com/articles/s41551-026-01651-5"><em>Nature Biomedical Engineering</em></a>, were so compelling that they spurred Liu to recommend using the same deaminase in <a target="_blank" href="https://www.nejm.org/doi/full/10.1056/NEJMoa2504747">KJ’s treatment</a> when the child’s doctors approached him in early 2025, even before the findings were published.</p> <p>In the new study, Liu and his team, in collaboration with scientists led by Cat Lutz at the Jackson Laboratory and Joe Hacia at USC, showed that base editing can correct mutations in the <em>PEX1</em> gene that cause Zellweger spectrum disorder , a rare, life-threatening condition that leads to liver and brain damage and is unrelated to KJ’s disease. The team demonstrated that this base edit, when made in a mouse model of the disorder, restored function of the liver and of peroxisomes — tiny fluid-filled sacs in cells that break down metabolic byproducts but are impaired as a result of the <em>PEX1</em> mutation. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Learn more</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Portrait of David Liu"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=glIu3Ovm 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql" alt="Portrait of David Liu" title="Portrait of David Liu" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/prime-editing-treats-childhood-brain-disease-mice" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=SoaktP-I 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ" alt="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" title="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Prime editing treats childhood brain disease in mice</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=QhzrPs_f 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single prime editing system could potentially treat multiple genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=m6KRxf-E 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ" alt="Susanna M. Hamilton, ӳ����ý Communications" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">More versatile and efficient base editor unlocks new gene-editing targets</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The authors tested two different base editors in mice — one called ABE8e and a modified version called ABE8e-V106W — and found that both efficiently corrected the <em>PEX1</em> mutation, but ABE8e-V106W was significantly better tolerated in the animals and made fewer off-target edits. When Kiran Musunuru of the University of Pennsylvania Perelman School of Medicine, one of baby KJ’s lead doctors, asked Liu which deaminase he and his team should use to correct KJ’s disease-causing mutation, Liu recommended ABE8e-V106W based on the data reported in today’s publication.</p> <p>“These observations, well before the data was published, suggested that ABE8e-V106W is an adenine base editor that sits in the Goldilocks zone, where it offers both high on-target activity that can efficiently correct a pathogenic mutation, and relatively low off-target activity that reduces the frequency of unwanted edits,” said <a target="_blank" href="/bios/david-liu">Liu</a>, Richard Merkin Professor, and director of the <a target="_blank" href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute for Transformative Technologies in Healthcare</a> at ӳ����ý the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>“It’s easy to assume that rescuing this quite-rare peroxisome disorder in mice wouldn’t have anything to do with saving a human baby with a very different life-threatening disease. But, it actually had a lot to do with it. It goes to show how science builds on itself, and how sharing the latest unpublished findings at a key moment can inform important decisions in the cutting-edge treatment of patients,” Liu added.</p> <p>The findings pave a path toward treating the root genetic cause of Zellweger spectrum disorder, a metabolic disease that affects about 1 in 50,000 to 90,000 births in North America.</p> <p>“Correcting the most common <em>PEX1</em> mutation is just the beginning of building meaningful treatment strategies for patients with Zellweger spectrum disorder, who currently have no options that treat the cause of the disease,” said lead author <a target="_blank" href="https://www.ophthalmology.pitt.edu/people/xin-daniel-gao-phd">Xin “Daniel” Gao</a>, now an Assistant Professor at the University of Pittsburgh, who led the project as a postdoctoral fellow in Liu’s lab. “More broadly, this work lays the foundation for using precision gene editing to develop better treatments for other rare peroxisomal diseases caused by mutations in PEX genes.”</p> <p>“A great deal of work went into the mouse modeling for this project. Ultimately, we developed a model that faithfully reproduces the disease and its long-chain fatty acid biomarkers, giving us strong confidence that these findings will translate into the clinic. This collaboration between David’s and my labs represents one of many joint efforts and serves as a cornerstone for future therapeutic advances emerging from the Center for Genetic Surgery,” said <a target="_blank" href="https://www.jax.org/research-and-faculty/faculty/research-scientists/cat-lutz">Lutz</a>, co-senior author of the study and vice president of the Rare Disease Translational Center at Jackson Laboratory.</p> <p><strong>Translational potential </strong> </p> <p>In their study, the researchers administered base editors to neonatal and older mice with the <em>PEX1</em> variant, using two adeno-associated viruses, which delivered the base editors to the livers of the animals. The team revealed that the base editor corrected the <em>PEX1</em> gene in roughly 60 percent of liver cells, high enough to restore peroxisome and liver function and lower the buildup of toxic metabolites throughout the body.</p> <p>The scientists also showed that the editing efficiency increased over the duration of the study — a lower dose of base editors was able to achieve the same level of editing over time as the higher dose the team tested.</p> <p>According to Liu, more research is needed to translate this work in mice into a potential treatment for humans. For example, the authors showed that the base editing system could be reformulated to be delivered using lipid nanoparticles, which have been used in several treatments for humans including KJ’s. However, further optimization of nanoparticle delivery of the base editor to treat Zellweger spectrum disorder (ZSD) remains to be done.</p> <p>One of Liu’s ultimate goals is to make personalized gene editing treatments accessible to patients on a broader scale through the new Center for Genetic Surgery (CGS) that he co-leads at ӳ����ý.</p> <p>“Currently, candidate CGS programs are ones for which a base or prime editor has been shown to correct a pathogenic mutation back to a healthy sequence, resulting in at least partial rescue of the disease in an animal model,” Liu said. “Demonstrating benefit to animals provides the foundation to move the study towards a clinical trial that we hope will eventually benefit patients with few treatment options.”</p> <p>“There is an urgent unmet need to develop and implement targeted therapies that address the root causes of thousands of genetic disorders. I am honored that our work on a common form of ZSD may have broader impact across other genetic diseases,” said <a target="_blank" href="https://keck.usc.edu/faculty-search/joseph-g-hacia/">Hacia</a>, co-senior author and medical geneticist at the Keck School of Medicine of University of Southern California. “Many children with ZSD develop life-threatening liver disease, leading to frequent hospitalizations and a shortened lifespan. We are driven by the hope of changing that reality and look forward to advancing this work into clinical trials to address liver disease in ZSD and related pathologies in other affected organs.”</p> <p>The study’s co-first authors are Xin “Daniel” Gao of ӳ����ý and Maximiliano Presa of Jackson Laboratory, and other co-authors include Nancy Braverman of McGill University and Guangping Gao of University of Massachusetts Chan Medical School.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health, the Global Foundation for Peroxisomal Disorders, and Wynne Mateffy Research Foundation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Gao XD, Presa M, et al. <a href="https://www.nature.com/articles/s41551-026-01651-5" target="_blank">In vivo base editing rescues liver pathophysiology and peroxisome dysfunction in a mouse model of Zellweger spectrum disorder</a>. <em>Nature Biomedical Engineering</em>. Online April 14, 2026. DOI: 10.1038/s41551-026-01651-5<br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/gene-editing" hreflang="en">Gene editing</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Tue, 14 Apr 2026 13:00:00 +0000 jcolaros 5560371 at /news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" class="datetime">April 14, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The base editing enzyme used in this study is the same one that fixed Baby KJ Muldoon’s disease-causing mutation and saved his life in 2025.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" title="Tuesday, April 14, 2026 - 09:00" class="datetime">April 14, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A letter C is penciled into a long DNA sequence. "> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=x65fUlJp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=bcuAAMZD 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=WwHaTNVb 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy" alt="A letter C is penciled into a long DNA sequence. " title="A letter C is penciled into a long DNA sequence. " typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Susanna Hamilton </div> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/2196/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2196/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2196/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li data-list-item-id="e8d1325b084ac3c4798f4fe8846f1bfbc">Zellweger spectrum disorder is a group of genetic conditions that affect multiple organs in the body and the most severe form can be fatal in the first year of life.</li> <li aria-level="1" data-list-item-id="ee50c6be27935e16cc0c6f58877166496">Scientists used base editing to correct a disease-causing mutation in the <em>PEX1</em> gene in human cells and mice. This restored the function of peroxisomes, an organelle in the cell that malfunctions in these disorders.</li> <li aria-level="1" data-list-item-id="e345218bc482a038c22e0d62b5b42253a">The study, which began in 2020, guided the team to focus on a key base editor component — a deaminase enzyme — that was subsequently used to treat baby KJ Muldoon with a different genetic disease in 2025.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>In 2025, baby KJ Muldoon <a target="_blank" href="https://www.chop.edu/news/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital">became the first person</a> to receive a personalized gene editing treatment, which likely saved his life. But the scientific advances that made the groundbreaking treatment possible were years in the making long before KJ was born. One was base editing, the technology developed in 2016 by David Liu and his lab at the ӳ����ý that makes single-letter changes in DNA and was used to correct KJ’s life-threatening mutation.  </p> <p>Another advancement was the development and characterization of a specific version of a key base editor component: the enzyme called a deaminase, which converts a disease-causing DNA letter into a healthy one. Efforts to identify an optimal deaminase for a different genetic disorder began in 2020 in a collaboration between Liu’s lab and scientists from Jackson Laboratory and the University of Southern California (USC). The results of this project, published today in <a target="_blank" href="https://www.nature.com/articles/s41551-026-01651-5"><em>Nature Biomedical Engineering</em></a>, were so compelling that they spurred Liu to recommend using the same deaminase in <a target="_blank" href="https://www.nejm.org/doi/full/10.1056/NEJMoa2504747">KJ’s treatment</a> when the child’s doctors approached him in early 2025, even before the findings were published.</p> <p>In the new study, Liu and his team, in collaboration with scientists led by Cat Lutz at the Jackson Laboratory and Joe Hacia at USC, showed that base editing can correct mutations in the <em>PEX1</em> gene that cause Zellweger spectrum disorder , a rare, life-threatening condition that leads to liver and brain damage and is unrelated to KJ’s disease. The team demonstrated that this base edit, when made in a mouse model of the disorder, restored function of the liver and of peroxisomes — tiny fluid-filled sacs in cells that break down metabolic byproducts but are impaired as a result of the <em>PEX1</em> mutation. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Learn more</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Portrait of David Liu"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=glIu3Ovm 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql" alt="Portrait of David Liu" title="Portrait of David Liu" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/prime-editing-treats-childhood-brain-disease-mice" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=SoaktP-I 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ" alt="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" title="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Prime editing treats childhood brain disease in mice</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=QhzrPs_f 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single prime editing system could potentially treat multiple genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=m6KRxf-E 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ" alt="Susanna M. Hamilton, ӳ����ý Communications" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">More versatile and efficient base editor unlocks new gene-editing targets</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The authors tested two different base editors in mice — one called ABE8e and a modified version called ABE8e-V106W — and found that both efficiently corrected the <em>PEX1</em> mutation, but ABE8e-V106W was significantly better tolerated in the animals and made fewer off-target edits. When Kiran Musunuru of the University of Pennsylvania Perelman School of Medicine, one of baby KJ’s lead doctors, asked Liu which deaminase he and his team should use to correct KJ’s disease-causing mutation, Liu recommended ABE8e-V106W based on the data reported in today’s publication.</p> <p>“These observations, well before the data was published, suggested that ABE8e-V106W is an adenine base editor that sits in the Goldilocks zone, where it offers both high on-target activity that can efficiently correct a pathogenic mutation, and relatively low off-target activity that reduces the frequency of unwanted edits,” said <a target="_blank" href="/bios/david-liu">Liu</a>, Richard Merkin Professor, and director of the <a target="_blank" href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute for Transformative Technologies in Healthcare</a> at ӳ����ý the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>“It’s easy to assume that rescuing this quite-rare peroxisome disorder in mice wouldn’t have anything to do with saving a human baby with a very different life-threatening disease. But, it actually had a lot to do with it. It goes to show how science builds on itself, and how sharing the latest unpublished findings at a key moment can inform important decisions in the cutting-edge treatment of patients,” Liu added.</p> <p>The findings pave a path toward treating the root genetic cause of Zellweger spectrum disorder, a metabolic disease that affects about 1 in 50,000 to 90,000 births in North America.</p> <p>“Correcting the most common <em>PEX1</em> mutation is just the beginning of building meaningful treatment strategies for patients with Zellweger spectrum disorder, who currently have no options that treat the cause of the disease,” said lead author <a target="_blank" href="https://www.ophthalmology.pitt.edu/people/xin-daniel-gao-phd">Xin “Daniel” Gao</a>, now an Assistant Professor at the University of Pittsburgh, who led the project as a postdoctoral fellow in Liu’s lab. “More broadly, this work lays the foundation for using precision gene editing to develop better treatments for other rare peroxisomal diseases caused by mutations in PEX genes.”</p> <p>“A great deal of work went into the mouse modeling for this project. Ultimately, we developed a model that faithfully reproduces the disease and its long-chain fatty acid biomarkers, giving us strong confidence that these findings will translate into the clinic. This collaboration between David’s and my labs represents one of many joint efforts and serves as a cornerstone for future therapeutic advances emerging from the Center for Genetic Surgery,” said <a target="_blank" href="https://www.jax.org/research-and-faculty/faculty/research-scientists/cat-lutz">Lutz</a>, co-senior author of the study and vice president of the Rare Disease Translational Center at Jackson Laboratory.</p> <p><strong>Translational potential </strong> </p> <p>In their study, the researchers administered base editors to neonatal and older mice with the <em>PEX1</em> variant, using two adeno-associated viruses, which delivered the base editors to the livers of the animals. The team revealed that the base editor corrected the <em>PEX1</em> gene in roughly 60 percent of liver cells, high enough to restore peroxisome and liver function and lower the buildup of toxic metabolites throughout the body.</p> <p>The scientists also showed that the editing efficiency increased over the duration of the study — a lower dose of base editors was able to achieve the same level of editing over time as the higher dose the team tested.</p> <p>According to Liu, more research is needed to translate this work in mice into a potential treatment for humans. For example, the authors showed that the base editing system could be reformulated to be delivered using lipid nanoparticles, which have been used in several treatments for humans including KJ’s. However, further optimization of nanoparticle delivery of the base editor to treat Zellweger spectrum disorder (ZSD) remains to be done.</p> <p>One of Liu’s ultimate goals is to make personalized gene editing treatments accessible to patients on a broader scale through the new Center for Genetic Surgery (CGS) that he co-leads at ӳ����ý.</p> <p>“Currently, candidate CGS programs are ones for which a base or prime editor has been shown to correct a pathogenic mutation back to a healthy sequence, resulting in at least partial rescue of the disease in an animal model,” Liu said. “Demonstrating benefit to animals provides the foundation to move the study towards a clinical trial that we hope will eventually benefit patients with few treatment options.”</p> <p>“There is an urgent unmet need to develop and implement targeted therapies that address the root causes of thousands of genetic disorders. I am honored that our work on a common form of ZSD may have broader impact across other genetic diseases,” said <a target="_blank" href="https://keck.usc.edu/faculty-search/joseph-g-hacia/">Hacia</a>, co-senior author and medical geneticist at the Keck School of Medicine of University of Southern California. “Many children with ZSD develop life-threatening liver disease, leading to frequent hospitalizations and a shortened lifespan. We are driven by the hope of changing that reality and look forward to advancing this work into clinical trials to address liver disease in ZSD and related pathologies in other affected organs.”</p> <p>The study’s co-first authors are Xin “Daniel” Gao of ӳ����ý and Maximiliano Presa of Jackson Laboratory, and other co-authors include Nancy Braverman of McGill University and Guangping Gao of University of Massachusetts Chan Medical School.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health, the Global Foundation for Peroxisomal Disorders, and Wynne Mateffy Research Foundation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Gao XD, Presa M, et al. <a href="https://www.nature.com/articles/s41551-026-01651-5" target="_blank">In vivo base editing rescues liver pathophysiology and peroxisome dysfunction in a mouse model of Zellweger spectrum disorder</a>. <em>Nature Biomedical Engineering</em>. Online April 14, 2026. DOI: 10.1038/s41551-026-01651-5<br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/gene-editing" hreflang="en">Gene editing</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Wed, 19 Nov 2025 17:01:34 +0000 kzusi@broadinstitute.org 5559721 at /news/prime-editing-treats-childhood-brain-disease-mice <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" class="datetime">April 14, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The base editing enzyme used in this study is the same one that fixed Baby KJ Muldoon’s disease-causing mutation and saved his life in 2025.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" title="Tuesday, April 14, 2026 - 09:00" class="datetime">April 14, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A letter C is penciled into a long DNA sequence. "> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=x65fUlJp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=bcuAAMZD 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=WwHaTNVb 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy" alt="A letter C is penciled into a long DNA sequence. " title="A letter C is penciled into a long DNA sequence. " typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Susanna Hamilton </div> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/2196/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2196/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2196/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li data-list-item-id="e8d1325b084ac3c4798f4fe8846f1bfbc">Zellweger spectrum disorder is a group of genetic conditions that affect multiple organs in the body and the most severe form can be fatal in the first year of life.</li> <li aria-level="1" data-list-item-id="ee50c6be27935e16cc0c6f58877166496">Scientists used base editing to correct a disease-causing mutation in the <em>PEX1</em> gene in human cells and mice. This restored the function of peroxisomes, an organelle in the cell that malfunctions in these disorders.</li> <li aria-level="1" data-list-item-id="e345218bc482a038c22e0d62b5b42253a">The study, which began in 2020, guided the team to focus on a key base editor component — a deaminase enzyme — that was subsequently used to treat baby KJ Muldoon with a different genetic disease in 2025.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>In 2025, baby KJ Muldoon <a target="_blank" href="https://www.chop.edu/news/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital">became the first person</a> to receive a personalized gene editing treatment, which likely saved his life. But the scientific advances that made the groundbreaking treatment possible were years in the making long before KJ was born. One was base editing, the technology developed in 2016 by David Liu and his lab at the ӳ����ý that makes single-letter changes in DNA and was used to correct KJ’s life-threatening mutation.  </p> <p>Another advancement was the development and characterization of a specific version of a key base editor component: the enzyme called a deaminase, which converts a disease-causing DNA letter into a healthy one. Efforts to identify an optimal deaminase for a different genetic disorder began in 2020 in a collaboration between Liu’s lab and scientists from Jackson Laboratory and the University of Southern California (USC). The results of this project, published today in <a target="_blank" href="https://www.nature.com/articles/s41551-026-01651-5"><em>Nature Biomedical Engineering</em></a>, were so compelling that they spurred Liu to recommend using the same deaminase in <a target="_blank" href="https://www.nejm.org/doi/full/10.1056/NEJMoa2504747">KJ’s treatment</a> when the child’s doctors approached him in early 2025, even before the findings were published.</p> <p>In the new study, Liu and his team, in collaboration with scientists led by Cat Lutz at the Jackson Laboratory and Joe Hacia at USC, showed that base editing can correct mutations in the <em>PEX1</em> gene that cause Zellweger spectrum disorder , a rare, life-threatening condition that leads to liver and brain damage and is unrelated to KJ’s disease. The team demonstrated that this base edit, when made in a mouse model of the disorder, restored function of the liver and of peroxisomes — tiny fluid-filled sacs in cells that break down metabolic byproducts but are impaired as a result of the <em>PEX1</em> mutation. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Learn more</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Portrait of David Liu"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=glIu3Ovm 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql" alt="Portrait of David Liu" title="Portrait of David Liu" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/prime-editing-treats-childhood-brain-disease-mice" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=SoaktP-I 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ" alt="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" title="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Prime editing treats childhood brain disease in mice</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=QhzrPs_f 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single prime editing system could potentially treat multiple genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=m6KRxf-E 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ" alt="Susanna M. Hamilton, ӳ����ý Communications" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">More versatile and efficient base editor unlocks new gene-editing targets</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The authors tested two different base editors in mice — one called ABE8e and a modified version called ABE8e-V106W — and found that both efficiently corrected the <em>PEX1</em> mutation, but ABE8e-V106W was significantly better tolerated in the animals and made fewer off-target edits. When Kiran Musunuru of the University of Pennsylvania Perelman School of Medicine, one of baby KJ’s lead doctors, asked Liu which deaminase he and his team should use to correct KJ’s disease-causing mutation, Liu recommended ABE8e-V106W based on the data reported in today’s publication.</p> <p>“These observations, well before the data was published, suggested that ABE8e-V106W is an adenine base editor that sits in the Goldilocks zone, where it offers both high on-target activity that can efficiently correct a pathogenic mutation, and relatively low off-target activity that reduces the frequency of unwanted edits,” said <a target="_blank" href="/bios/david-liu">Liu</a>, Richard Merkin Professor, and director of the <a target="_blank" href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute for Transformative Technologies in Healthcare</a> at ӳ����ý the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>“It’s easy to assume that rescuing this quite-rare peroxisome disorder in mice wouldn’t have anything to do with saving a human baby with a very different life-threatening disease. But, it actually had a lot to do with it. It goes to show how science builds on itself, and how sharing the latest unpublished findings at a key moment can inform important decisions in the cutting-edge treatment of patients,” Liu added.</p> <p>The findings pave a path toward treating the root genetic cause of Zellweger spectrum disorder, a metabolic disease that affects about 1 in 50,000 to 90,000 births in North America.</p> <p>“Correcting the most common <em>PEX1</em> mutation is just the beginning of building meaningful treatment strategies for patients with Zellweger spectrum disorder, who currently have no options that treat the cause of the disease,” said lead author <a target="_blank" href="https://www.ophthalmology.pitt.edu/people/xin-daniel-gao-phd">Xin “Daniel” Gao</a>, now an Assistant Professor at the University of Pittsburgh, who led the project as a postdoctoral fellow in Liu’s lab. “More broadly, this work lays the foundation for using precision gene editing to develop better treatments for other rare peroxisomal diseases caused by mutations in PEX genes.”</p> <p>“A great deal of work went into the mouse modeling for this project. Ultimately, we developed a model that faithfully reproduces the disease and its long-chain fatty acid biomarkers, giving us strong confidence that these findings will translate into the clinic. This collaboration between David’s and my labs represents one of many joint efforts and serves as a cornerstone for future therapeutic advances emerging from the Center for Genetic Surgery,” said <a target="_blank" href="https://www.jax.org/research-and-faculty/faculty/research-scientists/cat-lutz">Lutz</a>, co-senior author of the study and vice president of the Rare Disease Translational Center at Jackson Laboratory.</p> <p><strong>Translational potential </strong> </p> <p>In their study, the researchers administered base editors to neonatal and older mice with the <em>PEX1</em> variant, using two adeno-associated viruses, which delivered the base editors to the livers of the animals. The team revealed that the base editor corrected the <em>PEX1</em> gene in roughly 60 percent of liver cells, high enough to restore peroxisome and liver function and lower the buildup of toxic metabolites throughout the body.</p> <p>The scientists also showed that the editing efficiency increased over the duration of the study — a lower dose of base editors was able to achieve the same level of editing over time as the higher dose the team tested.</p> <p>According to Liu, more research is needed to translate this work in mice into a potential treatment for humans. For example, the authors showed that the base editing system could be reformulated to be delivered using lipid nanoparticles, which have been used in several treatments for humans including KJ’s. However, further optimization of nanoparticle delivery of the base editor to treat Zellweger spectrum disorder (ZSD) remains to be done.</p> <p>One of Liu’s ultimate goals is to make personalized gene editing treatments accessible to patients on a broader scale through the new Center for Genetic Surgery (CGS) that he co-leads at ӳ����ý.</p> <p>“Currently, candidate CGS programs are ones for which a base or prime editor has been shown to correct a pathogenic mutation back to a healthy sequence, resulting in at least partial rescue of the disease in an animal model,” Liu said. “Demonstrating benefit to animals provides the foundation to move the study towards a clinical trial that we hope will eventually benefit patients with few treatment options.”</p> <p>“There is an urgent unmet need to develop and implement targeted therapies that address the root causes of thousands of genetic disorders. I am honored that our work on a common form of ZSD may have broader impact across other genetic diseases,” said <a target="_blank" href="https://keck.usc.edu/faculty-search/joseph-g-hacia/">Hacia</a>, co-senior author and medical geneticist at the Keck School of Medicine of University of Southern California. “Many children with ZSD develop life-threatening liver disease, leading to frequent hospitalizations and a shortened lifespan. We are driven by the hope of changing that reality and look forward to advancing this work into clinical trials to address liver disease in ZSD and related pathologies in other affected organs.”</p> <p>The study’s co-first authors are Xin “Daniel” Gao of ӳ����ý and Maximiliano Presa of Jackson Laboratory, and other co-authors include Nancy Braverman of McGill University and Guangping Gao of University of Massachusetts Chan Medical School.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health, the Global Foundation for Peroxisomal Disorders, and Wynne Mateffy Research Foundation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Gao XD, Presa M, et al. <a href="https://www.nature.com/articles/s41551-026-01651-5" target="_blank">In vivo base editing rescues liver pathophysiology and peroxisome dysfunction in a mouse model of Zellweger spectrum disorder</a>. <em>Nature Biomedical Engineering</em>. Online April 14, 2026. DOI: 10.1038/s41551-026-01651-5<br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/gene-editing" hreflang="en">Gene editing</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Mon, 21 Jul 2025 15:37:05 +0000 Corie Lok 5559001 at /news/gene-editing-disrupts-huntingtons-mutation-mice <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" class="datetime">April 14, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The base editing enzyme used in this study is the same one that fixed Baby KJ Muldoon’s disease-causing mutation and saved his life in 2025.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" title="Tuesday, April 14, 2026 - 09:00" class="datetime">April 14, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A letter C is penciled into a long DNA sequence. "> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=x65fUlJp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=bcuAAMZD 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=WwHaTNVb 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy" alt="A letter C is penciled into a long DNA sequence. " title="A letter C is penciled into a long DNA sequence. " typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Susanna Hamilton </div> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/2196/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2196/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2196/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li data-list-item-id="e8d1325b084ac3c4798f4fe8846f1bfbc">Zellweger spectrum disorder is a group of genetic conditions that affect multiple organs in the body and the most severe form can be fatal in the first year of life.</li> <li aria-level="1" data-list-item-id="ee50c6be27935e16cc0c6f58877166496">Scientists used base editing to correct a disease-causing mutation in the <em>PEX1</em> gene in human cells and mice. This restored the function of peroxisomes, an organelle in the cell that malfunctions in these disorders.</li> <li aria-level="1" data-list-item-id="e345218bc482a038c22e0d62b5b42253a">The study, which began in 2020, guided the team to focus on a key base editor component — a deaminase enzyme — that was subsequently used to treat baby KJ Muldoon with a different genetic disease in 2025.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>In 2025, baby KJ Muldoon <a target="_blank" href="https://www.chop.edu/news/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital">became the first person</a> to receive a personalized gene editing treatment, which likely saved his life. But the scientific advances that made the groundbreaking treatment possible were years in the making long before KJ was born. One was base editing, the technology developed in 2016 by David Liu and his lab at the ӳ����ý that makes single-letter changes in DNA and was used to correct KJ’s life-threatening mutation.  </p> <p>Another advancement was the development and characterization of a specific version of a key base editor component: the enzyme called a deaminase, which converts a disease-causing DNA letter into a healthy one. Efforts to identify an optimal deaminase for a different genetic disorder began in 2020 in a collaboration between Liu’s lab and scientists from Jackson Laboratory and the University of Southern California (USC). The results of this project, published today in <a target="_blank" href="https://www.nature.com/articles/s41551-026-01651-5"><em>Nature Biomedical Engineering</em></a>, were so compelling that they spurred Liu to recommend using the same deaminase in <a target="_blank" href="https://www.nejm.org/doi/full/10.1056/NEJMoa2504747">KJ’s treatment</a> when the child’s doctors approached him in early 2025, even before the findings were published.</p> <p>In the new study, Liu and his team, in collaboration with scientists led by Cat Lutz at the Jackson Laboratory and Joe Hacia at USC, showed that base editing can correct mutations in the <em>PEX1</em> gene that cause Zellweger spectrum disorder , a rare, life-threatening condition that leads to liver and brain damage and is unrelated to KJ’s disease. The team demonstrated that this base edit, when made in a mouse model of the disorder, restored function of the liver and of peroxisomes — tiny fluid-filled sacs in cells that break down metabolic byproducts but are impaired as a result of the <em>PEX1</em> mutation. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Learn more</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Portrait of David Liu"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=glIu3Ovm 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql" alt="Portrait of David Liu" title="Portrait of David Liu" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/prime-editing-treats-childhood-brain-disease-mice" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=SoaktP-I 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ" alt="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" title="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Prime editing treats childhood brain disease in mice</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=QhzrPs_f 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single prime editing system could potentially treat multiple genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=m6KRxf-E 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ" alt="Susanna M. Hamilton, ӳ����ý Communications" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">More versatile and efficient base editor unlocks new gene-editing targets</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The authors tested two different base editors in mice — one called ABE8e and a modified version called ABE8e-V106W — and found that both efficiently corrected the <em>PEX1</em> mutation, but ABE8e-V106W was significantly better tolerated in the animals and made fewer off-target edits. When Kiran Musunuru of the University of Pennsylvania Perelman School of Medicine, one of baby KJ’s lead doctors, asked Liu which deaminase he and his team should use to correct KJ’s disease-causing mutation, Liu recommended ABE8e-V106W based on the data reported in today’s publication.</p> <p>“These observations, well before the data was published, suggested that ABE8e-V106W is an adenine base editor that sits in the Goldilocks zone, where it offers both high on-target activity that can efficiently correct a pathogenic mutation, and relatively low off-target activity that reduces the frequency of unwanted edits,” said <a target="_blank" href="/bios/david-liu">Liu</a>, Richard Merkin Professor, and director of the <a target="_blank" href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute for Transformative Technologies in Healthcare</a> at ӳ����ý the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>“It’s easy to assume that rescuing this quite-rare peroxisome disorder in mice wouldn’t have anything to do with saving a human baby with a very different life-threatening disease. But, it actually had a lot to do with it. It goes to show how science builds on itself, and how sharing the latest unpublished findings at a key moment can inform important decisions in the cutting-edge treatment of patients,” Liu added.</p> <p>The findings pave a path toward treating the root genetic cause of Zellweger spectrum disorder, a metabolic disease that affects about 1 in 50,000 to 90,000 births in North America.</p> <p>“Correcting the most common <em>PEX1</em> mutation is just the beginning of building meaningful treatment strategies for patients with Zellweger spectrum disorder, who currently have no options that treat the cause of the disease,” said lead author <a target="_blank" href="https://www.ophthalmology.pitt.edu/people/xin-daniel-gao-phd">Xin “Daniel” Gao</a>, now an Assistant Professor at the University of Pittsburgh, who led the project as a postdoctoral fellow in Liu’s lab. “More broadly, this work lays the foundation for using precision gene editing to develop better treatments for other rare peroxisomal diseases caused by mutations in PEX genes.”</p> <p>“A great deal of work went into the mouse modeling for this project. Ultimately, we developed a model that faithfully reproduces the disease and its long-chain fatty acid biomarkers, giving us strong confidence that these findings will translate into the clinic. This collaboration between David’s and my labs represents one of many joint efforts and serves as a cornerstone for future therapeutic advances emerging from the Center for Genetic Surgery,” said <a target="_blank" href="https://www.jax.org/research-and-faculty/faculty/research-scientists/cat-lutz">Lutz</a>, co-senior author of the study and vice president of the Rare Disease Translational Center at Jackson Laboratory.</p> <p><strong>Translational potential </strong> </p> <p>In their study, the researchers administered base editors to neonatal and older mice with the <em>PEX1</em> variant, using two adeno-associated viruses, which delivered the base editors to the livers of the animals. The team revealed that the base editor corrected the <em>PEX1</em> gene in roughly 60 percent of liver cells, high enough to restore peroxisome and liver function and lower the buildup of toxic metabolites throughout the body.</p> <p>The scientists also showed that the editing efficiency increased over the duration of the study — a lower dose of base editors was able to achieve the same level of editing over time as the higher dose the team tested.</p> <p>According to Liu, more research is needed to translate this work in mice into a potential treatment for humans. For example, the authors showed that the base editing system could be reformulated to be delivered using lipid nanoparticles, which have been used in several treatments for humans including KJ’s. However, further optimization of nanoparticle delivery of the base editor to treat Zellweger spectrum disorder (ZSD) remains to be done.</p> <p>One of Liu’s ultimate goals is to make personalized gene editing treatments accessible to patients on a broader scale through the new Center for Genetic Surgery (CGS) that he co-leads at ӳ����ý.</p> <p>“Currently, candidate CGS programs are ones for which a base or prime editor has been shown to correct a pathogenic mutation back to a healthy sequence, resulting in at least partial rescue of the disease in an animal model,” Liu said. “Demonstrating benefit to animals provides the foundation to move the study towards a clinical trial that we hope will eventually benefit patients with few treatment options.”</p> <p>“There is an urgent unmet need to develop and implement targeted therapies that address the root causes of thousands of genetic disorders. I am honored that our work on a common form of ZSD may have broader impact across other genetic diseases,” said <a target="_blank" href="https://keck.usc.edu/faculty-search/joseph-g-hacia/">Hacia</a>, co-senior author and medical geneticist at the Keck School of Medicine of University of Southern California. “Many children with ZSD develop life-threatening liver disease, leading to frequent hospitalizations and a shortened lifespan. We are driven by the hope of changing that reality and look forward to advancing this work into clinical trials to address liver disease in ZSD and related pathologies in other affected organs.”</p> <p>The study’s co-first authors are Xin “Daniel” Gao of ӳ����ý and Maximiliano Presa of Jackson Laboratory, and other co-authors include Nancy Braverman of McGill University and Guangping Gao of University of Massachusetts Chan Medical School.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health, the Global Foundation for Peroxisomal Disorders, and Wynne Mateffy Research Foundation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Gao XD, Presa M, et al. <a href="https://www.nature.com/articles/s41551-026-01651-5" target="_blank">In vivo base editing rescues liver pathophysiology and peroxisome dysfunction in a mouse model of Zellweger spectrum disorder</a>. <em>Nature Biomedical Engineering</em>. Online April 14, 2026. DOI: 10.1038/s41551-026-01651-5<br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/gene-editing" hreflang="en">Gene editing</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Tue, 27 May 2025 13:00:00 +0000 adicorat 5558521 at /news/evolved-gene-editor-inserts-entire-genes-human-cells <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" class="datetime">April 14, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The base editing enzyme used in this study is the same one that fixed Baby KJ Muldoon’s disease-causing mutation and saved his life in 2025.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" title="Tuesday, April 14, 2026 - 09:00" class="datetime">April 14, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A letter C is penciled into a long DNA sequence. "> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=x65fUlJp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=bcuAAMZD 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=WwHaTNVb 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy" alt="A letter C is penciled into a long DNA sequence. " title="A letter C is penciled into a long DNA sequence. " typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Susanna Hamilton </div> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/2196/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2196/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2196/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li data-list-item-id="e8d1325b084ac3c4798f4fe8846f1bfbc">Zellweger spectrum disorder is a group of genetic conditions that affect multiple organs in the body and the most severe form can be fatal in the first year of life.</li> <li aria-level="1" data-list-item-id="ee50c6be27935e16cc0c6f58877166496">Scientists used base editing to correct a disease-causing mutation in the <em>PEX1</em> gene in human cells and mice. This restored the function of peroxisomes, an organelle in the cell that malfunctions in these disorders.</li> <li aria-level="1" data-list-item-id="e345218bc482a038c22e0d62b5b42253a">The study, which began in 2020, guided the team to focus on a key base editor component — a deaminase enzyme — that was subsequently used to treat baby KJ Muldoon with a different genetic disease in 2025.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>In 2025, baby KJ Muldoon <a target="_blank" href="https://www.chop.edu/news/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital">became the first person</a> to receive a personalized gene editing treatment, which likely saved his life. But the scientific advances that made the groundbreaking treatment possible were years in the making long before KJ was born. One was base editing, the technology developed in 2016 by David Liu and his lab at the ӳ����ý that makes single-letter changes in DNA and was used to correct KJ’s life-threatening mutation.  </p> <p>Another advancement was the development and characterization of a specific version of a key base editor component: the enzyme called a deaminase, which converts a disease-causing DNA letter into a healthy one. Efforts to identify an optimal deaminase for a different genetic disorder began in 2020 in a collaboration between Liu’s lab and scientists from Jackson Laboratory and the University of Southern California (USC). The results of this project, published today in <a target="_blank" href="https://www.nature.com/articles/s41551-026-01651-5"><em>Nature Biomedical Engineering</em></a>, were so compelling that they spurred Liu to recommend using the same deaminase in <a target="_blank" href="https://www.nejm.org/doi/full/10.1056/NEJMoa2504747">KJ’s treatment</a> when the child’s doctors approached him in early 2025, even before the findings were published.</p> <p>In the new study, Liu and his team, in collaboration with scientists led by Cat Lutz at the Jackson Laboratory and Joe Hacia at USC, showed that base editing can correct mutations in the <em>PEX1</em> gene that cause Zellweger spectrum disorder , a rare, life-threatening condition that leads to liver and brain damage and is unrelated to KJ’s disease. The team demonstrated that this base edit, when made in a mouse model of the disorder, restored function of the liver and of peroxisomes — tiny fluid-filled sacs in cells that break down metabolic byproducts but are impaired as a result of the <em>PEX1</em> mutation. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Learn more</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Portrait of David Liu"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=glIu3Ovm 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql" alt="Portrait of David Liu" title="Portrait of David Liu" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/prime-editing-treats-childhood-brain-disease-mice" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=SoaktP-I 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ" alt="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" title="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Prime editing treats childhood brain disease in mice</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=QhzrPs_f 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single prime editing system could potentially treat multiple genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=m6KRxf-E 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ" alt="Susanna M. Hamilton, ӳ����ý Communications" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">More versatile and efficient base editor unlocks new gene-editing targets</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The authors tested two different base editors in mice — one called ABE8e and a modified version called ABE8e-V106W — and found that both efficiently corrected the <em>PEX1</em> mutation, but ABE8e-V106W was significantly better tolerated in the animals and made fewer off-target edits. When Kiran Musunuru of the University of Pennsylvania Perelman School of Medicine, one of baby KJ’s lead doctors, asked Liu which deaminase he and his team should use to correct KJ’s disease-causing mutation, Liu recommended ABE8e-V106W based on the data reported in today’s publication.</p> <p>“These observations, well before the data was published, suggested that ABE8e-V106W is an adenine base editor that sits in the Goldilocks zone, where it offers both high on-target activity that can efficiently correct a pathogenic mutation, and relatively low off-target activity that reduces the frequency of unwanted edits,” said <a target="_blank" href="/bios/david-liu">Liu</a>, Richard Merkin Professor, and director of the <a target="_blank" href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute for Transformative Technologies in Healthcare</a> at ӳ����ý the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>“It’s easy to assume that rescuing this quite-rare peroxisome disorder in mice wouldn’t have anything to do with saving a human baby with a very different life-threatening disease. But, it actually had a lot to do with it. It goes to show how science builds on itself, and how sharing the latest unpublished findings at a key moment can inform important decisions in the cutting-edge treatment of patients,” Liu added.</p> <p>The findings pave a path toward treating the root genetic cause of Zellweger spectrum disorder, a metabolic disease that affects about 1 in 50,000 to 90,000 births in North America.</p> <p>“Correcting the most common <em>PEX1</em> mutation is just the beginning of building meaningful treatment strategies for patients with Zellweger spectrum disorder, who currently have no options that treat the cause of the disease,” said lead author <a target="_blank" href="https://www.ophthalmology.pitt.edu/people/xin-daniel-gao-phd">Xin “Daniel” Gao</a>, now an Assistant Professor at the University of Pittsburgh, who led the project as a postdoctoral fellow in Liu’s lab. “More broadly, this work lays the foundation for using precision gene editing to develop better treatments for other rare peroxisomal diseases caused by mutations in PEX genes.”</p> <p>“A great deal of work went into the mouse modeling for this project. Ultimately, we developed a model that faithfully reproduces the disease and its long-chain fatty acid biomarkers, giving us strong confidence that these findings will translate into the clinic. This collaboration between David’s and my labs represents one of many joint efforts and serves as a cornerstone for future therapeutic advances emerging from the Center for Genetic Surgery,” said <a target="_blank" href="https://www.jax.org/research-and-faculty/faculty/research-scientists/cat-lutz">Lutz</a>, co-senior author of the study and vice president of the Rare Disease Translational Center at Jackson Laboratory.</p> <p><strong>Translational potential </strong> </p> <p>In their study, the researchers administered base editors to neonatal and older mice with the <em>PEX1</em> variant, using two adeno-associated viruses, which delivered the base editors to the livers of the animals. The team revealed that the base editor corrected the <em>PEX1</em> gene in roughly 60 percent of liver cells, high enough to restore peroxisome and liver function and lower the buildup of toxic metabolites throughout the body.</p> <p>The scientists also showed that the editing efficiency increased over the duration of the study — a lower dose of base editors was able to achieve the same level of editing over time as the higher dose the team tested.</p> <p>According to Liu, more research is needed to translate this work in mice into a potential treatment for humans. For example, the authors showed that the base editing system could be reformulated to be delivered using lipid nanoparticles, which have been used in several treatments for humans including KJ’s. However, further optimization of nanoparticle delivery of the base editor to treat Zellweger spectrum disorder (ZSD) remains to be done.</p> <p>One of Liu’s ultimate goals is to make personalized gene editing treatments accessible to patients on a broader scale through the new Center for Genetic Surgery (CGS) that he co-leads at ӳ����ý.</p> <p>“Currently, candidate CGS programs are ones for which a base or prime editor has been shown to correct a pathogenic mutation back to a healthy sequence, resulting in at least partial rescue of the disease in an animal model,” Liu said. “Demonstrating benefit to animals provides the foundation to move the study towards a clinical trial that we hope will eventually benefit patients with few treatment options.”</p> <p>“There is an urgent unmet need to develop and implement targeted therapies that address the root causes of thousands of genetic disorders. I am honored that our work on a common form of ZSD may have broader impact across other genetic diseases,” said <a target="_blank" href="https://keck.usc.edu/faculty-search/joseph-g-hacia/">Hacia</a>, co-senior author and medical geneticist at the Keck School of Medicine of University of Southern California. “Many children with ZSD develop life-threatening liver disease, leading to frequent hospitalizations and a shortened lifespan. We are driven by the hope of changing that reality and look forward to advancing this work into clinical trials to address liver disease in ZSD and related pathologies in other affected organs.”</p> <p>The study’s co-first authors are Xin “Daniel” Gao of ӳ����ý and Maximiliano Presa of Jackson Laboratory, and other co-authors include Nancy Braverman of McGill University and Guangping Gao of University of Massachusetts Chan Medical School.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health, the Global Foundation for Peroxisomal Disorders, and Wynne Mateffy Research Foundation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Gao XD, Presa M, et al. <a href="https://www.nature.com/articles/s41551-026-01651-5" target="_blank">In vivo base editing rescues liver pathophysiology and peroxisome dysfunction in a mouse model of Zellweger spectrum disorder</a>. <em>Nature Biomedical Engineering</em>. Online April 14, 2026. DOI: 10.1038/s41551-026-01651-5<br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/gene-editing" hreflang="en">Gene editing</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Thu, 15 May 2025 18:00:00 +0000 adicorat 5558566 at /news/prime-editing-efficiently-corrects-cystic-fibrosis-mutation-human-lung-cells <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" class="datetime">April 14, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The base editing enzyme used in this study is the same one that fixed Baby KJ Muldoon’s disease-causing mutation and saved his life in 2025.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" title="Tuesday, April 14, 2026 - 09:00" class="datetime">April 14, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A letter C is penciled into a long DNA sequence. "> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=x65fUlJp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=bcuAAMZD 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=WwHaTNVb 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy" alt="A letter C is penciled into a long DNA sequence. " title="A letter C is penciled into a long DNA sequence. " typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Susanna Hamilton </div> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/2196/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2196/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2196/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li data-list-item-id="e8d1325b084ac3c4798f4fe8846f1bfbc">Zellweger spectrum disorder is a group of genetic conditions that affect multiple organs in the body and the most severe form can be fatal in the first year of life.</li> <li aria-level="1" data-list-item-id="ee50c6be27935e16cc0c6f58877166496">Scientists used base editing to correct a disease-causing mutation in the <em>PEX1</em> gene in human cells and mice. This restored the function of peroxisomes, an organelle in the cell that malfunctions in these disorders.</li> <li aria-level="1" data-list-item-id="e345218bc482a038c22e0d62b5b42253a">The study, which began in 2020, guided the team to focus on a key base editor component — a deaminase enzyme — that was subsequently used to treat baby KJ Muldoon with a different genetic disease in 2025.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>In 2025, baby KJ Muldoon <a target="_blank" href="https://www.chop.edu/news/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital">became the first person</a> to receive a personalized gene editing treatment, which likely saved his life. But the scientific advances that made the groundbreaking treatment possible were years in the making long before KJ was born. One was base editing, the technology developed in 2016 by David Liu and his lab at the ӳ����ý that makes single-letter changes in DNA and was used to correct KJ’s life-threatening mutation.  </p> <p>Another advancement was the development and characterization of a specific version of a key base editor component: the enzyme called a deaminase, which converts a disease-causing DNA letter into a healthy one. Efforts to identify an optimal deaminase for a different genetic disorder began in 2020 in a collaboration between Liu’s lab and scientists from Jackson Laboratory and the University of Southern California (USC). The results of this project, published today in <a target="_blank" href="https://www.nature.com/articles/s41551-026-01651-5"><em>Nature Biomedical Engineering</em></a>, were so compelling that they spurred Liu to recommend using the same deaminase in <a target="_blank" href="https://www.nejm.org/doi/full/10.1056/NEJMoa2504747">KJ’s treatment</a> when the child’s doctors approached him in early 2025, even before the findings were published.</p> <p>In the new study, Liu and his team, in collaboration with scientists led by Cat Lutz at the Jackson Laboratory and Joe Hacia at USC, showed that base editing can correct mutations in the <em>PEX1</em> gene that cause Zellweger spectrum disorder , a rare, life-threatening condition that leads to liver and brain damage and is unrelated to KJ’s disease. The team demonstrated that this base edit, when made in a mouse model of the disorder, restored function of the liver and of peroxisomes — tiny fluid-filled sacs in cells that break down metabolic byproducts but are impaired as a result of the <em>PEX1</em> mutation. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Learn more</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Portrait of David Liu"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=glIu3Ovm 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql" alt="Portrait of David Liu" title="Portrait of David Liu" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/prime-editing-treats-childhood-brain-disease-mice" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=SoaktP-I 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ" alt="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" title="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Prime editing treats childhood brain disease in mice</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=QhzrPs_f 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single prime editing system could potentially treat multiple genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=m6KRxf-E 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ" alt="Susanna M. Hamilton, ӳ����ý Communications" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">More versatile and efficient base editor unlocks new gene-editing targets</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The authors tested two different base editors in mice — one called ABE8e and a modified version called ABE8e-V106W — and found that both efficiently corrected the <em>PEX1</em> mutation, but ABE8e-V106W was significantly better tolerated in the animals and made fewer off-target edits. When Kiran Musunuru of the University of Pennsylvania Perelman School of Medicine, one of baby KJ’s lead doctors, asked Liu which deaminase he and his team should use to correct KJ’s disease-causing mutation, Liu recommended ABE8e-V106W based on the data reported in today’s publication.</p> <p>“These observations, well before the data was published, suggested that ABE8e-V106W is an adenine base editor that sits in the Goldilocks zone, where it offers both high on-target activity that can efficiently correct a pathogenic mutation, and relatively low off-target activity that reduces the frequency of unwanted edits,” said <a target="_blank" href="/bios/david-liu">Liu</a>, Richard Merkin Professor, and director of the <a target="_blank" href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute for Transformative Technologies in Healthcare</a> at ӳ����ý the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>“It’s easy to assume that rescuing this quite-rare peroxisome disorder in mice wouldn’t have anything to do with saving a human baby with a very different life-threatening disease. But, it actually had a lot to do with it. It goes to show how science builds on itself, and how sharing the latest unpublished findings at a key moment can inform important decisions in the cutting-edge treatment of patients,” Liu added.</p> <p>The findings pave a path toward treating the root genetic cause of Zellweger spectrum disorder, a metabolic disease that affects about 1 in 50,000 to 90,000 births in North America.</p> <p>“Correcting the most common <em>PEX1</em> mutation is just the beginning of building meaningful treatment strategies for patients with Zellweger spectrum disorder, who currently have no options that treat the cause of the disease,” said lead author <a target="_blank" href="https://www.ophthalmology.pitt.edu/people/xin-daniel-gao-phd">Xin “Daniel” Gao</a>, now an Assistant Professor at the University of Pittsburgh, who led the project as a postdoctoral fellow in Liu’s lab. “More broadly, this work lays the foundation for using precision gene editing to develop better treatments for other rare peroxisomal diseases caused by mutations in PEX genes.”</p> <p>“A great deal of work went into the mouse modeling for this project. Ultimately, we developed a model that faithfully reproduces the disease and its long-chain fatty acid biomarkers, giving us strong confidence that these findings will translate into the clinic. This collaboration between David’s and my labs represents one of many joint efforts and serves as a cornerstone for future therapeutic advances emerging from the Center for Genetic Surgery,” said <a target="_blank" href="https://www.jax.org/research-and-faculty/faculty/research-scientists/cat-lutz">Lutz</a>, co-senior author of the study and vice president of the Rare Disease Translational Center at Jackson Laboratory.</p> <p><strong>Translational potential </strong> </p> <p>In their study, the researchers administered base editors to neonatal and older mice with the <em>PEX1</em> variant, using two adeno-associated viruses, which delivered the base editors to the livers of the animals. The team revealed that the base editor corrected the <em>PEX1</em> gene in roughly 60 percent of liver cells, high enough to restore peroxisome and liver function and lower the buildup of toxic metabolites throughout the body.</p> <p>The scientists also showed that the editing efficiency increased over the duration of the study — a lower dose of base editors was able to achieve the same level of editing over time as the higher dose the team tested.</p> <p>According to Liu, more research is needed to translate this work in mice into a potential treatment for humans. For example, the authors showed that the base editing system could be reformulated to be delivered using lipid nanoparticles, which have been used in several treatments for humans including KJ’s. However, further optimization of nanoparticle delivery of the base editor to treat Zellweger spectrum disorder (ZSD) remains to be done.</p> <p>One of Liu’s ultimate goals is to make personalized gene editing treatments accessible to patients on a broader scale through the new Center for Genetic Surgery (CGS) that he co-leads at ӳ����ý.</p> <p>“Currently, candidate CGS programs are ones for which a base or prime editor has been shown to correct a pathogenic mutation back to a healthy sequence, resulting in at least partial rescue of the disease in an animal model,” Liu said. “Demonstrating benefit to animals provides the foundation to move the study towards a clinical trial that we hope will eventually benefit patients with few treatment options.”</p> <p>“There is an urgent unmet need to develop and implement targeted therapies that address the root causes of thousands of genetic disorders. I am honored that our work on a common form of ZSD may have broader impact across other genetic diseases,” said <a target="_blank" href="https://keck.usc.edu/faculty-search/joseph-g-hacia/">Hacia</a>, co-senior author and medical geneticist at the Keck School of Medicine of University of Southern California. “Many children with ZSD develop life-threatening liver disease, leading to frequent hospitalizations and a shortened lifespan. We are driven by the hope of changing that reality and look forward to advancing this work into clinical trials to address liver disease in ZSD and related pathologies in other affected organs.”</p> <p>The study’s co-first authors are Xin “Daniel” Gao of ӳ����ý and Maximiliano Presa of Jackson Laboratory, and other co-authors include Nancy Braverman of McGill University and Guangping Gao of University of Massachusetts Chan Medical School.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health, the Global Foundation for Peroxisomal Disorders, and Wynne Mateffy Research Foundation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Gao XD, Presa M, et al. <a href="https://www.nature.com/articles/s41551-026-01651-5" target="_blank">In vivo base editing rescues liver pathophysiology and peroxisome dysfunction in a mouse model of Zellweger spectrum disorder</a>. <em>Nature Biomedical Engineering</em>. Online April 14, 2026. DOI: 10.1038/s41551-026-01651-5<br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/gene-editing" hreflang="en">Gene editing</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Wed, 10 Jul 2024 09:00:00 +0000 adicorat 5557111 at /news/improved-prime-editing-system-makes-gene-sized-edits-human-cells-therapeutic-levels <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" class="datetime">April 14, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The base editing enzyme used in this study is the same one that fixed Baby KJ Muldoon’s disease-causing mutation and saved his life in 2025.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" title="Tuesday, April 14, 2026 - 09:00" class="datetime">April 14, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A letter C is penciled into a long DNA sequence. "> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=x65fUlJp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=bcuAAMZD 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=WwHaTNVb 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy" alt="A letter C is penciled into a long DNA sequence. " title="A letter C is penciled into a long DNA sequence. " typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Susanna Hamilton </div> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/2196/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2196/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2196/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li data-list-item-id="e8d1325b084ac3c4798f4fe8846f1bfbc">Zellweger spectrum disorder is a group of genetic conditions that affect multiple organs in the body and the most severe form can be fatal in the first year of life.</li> <li aria-level="1" data-list-item-id="ee50c6be27935e16cc0c6f58877166496">Scientists used base editing to correct a disease-causing mutation in the <em>PEX1</em> gene in human cells and mice. This restored the function of peroxisomes, an organelle in the cell that malfunctions in these disorders.</li> <li aria-level="1" data-list-item-id="e345218bc482a038c22e0d62b5b42253a">The study, which began in 2020, guided the team to focus on a key base editor component — a deaminase enzyme — that was subsequently used to treat baby KJ Muldoon with a different genetic disease in 2025.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>In 2025, baby KJ Muldoon <a target="_blank" href="https://www.chop.edu/news/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital">became the first person</a> to receive a personalized gene editing treatment, which likely saved his life. But the scientific advances that made the groundbreaking treatment possible were years in the making long before KJ was born. One was base editing, the technology developed in 2016 by David Liu and his lab at the ӳ����ý that makes single-letter changes in DNA and was used to correct KJ’s life-threatening mutation.  </p> <p>Another advancement was the development and characterization of a specific version of a key base editor component: the enzyme called a deaminase, which converts a disease-causing DNA letter into a healthy one. Efforts to identify an optimal deaminase for a different genetic disorder began in 2020 in a collaboration between Liu’s lab and scientists from Jackson Laboratory and the University of Southern California (USC). The results of this project, published today in <a target="_blank" href="https://www.nature.com/articles/s41551-026-01651-5"><em>Nature Biomedical Engineering</em></a>, were so compelling that they spurred Liu to recommend using the same deaminase in <a target="_blank" href="https://www.nejm.org/doi/full/10.1056/NEJMoa2504747">KJ’s treatment</a> when the child’s doctors approached him in early 2025, even before the findings were published.</p> <p>In the new study, Liu and his team, in collaboration with scientists led by Cat Lutz at the Jackson Laboratory and Joe Hacia at USC, showed that base editing can correct mutations in the <em>PEX1</em> gene that cause Zellweger spectrum disorder , a rare, life-threatening condition that leads to liver and brain damage and is unrelated to KJ’s disease. The team demonstrated that this base edit, when made in a mouse model of the disorder, restored function of the liver and of peroxisomes — tiny fluid-filled sacs in cells that break down metabolic byproducts but are impaired as a result of the <em>PEX1</em> mutation. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Learn more</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Portrait of David Liu"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=glIu3Ovm 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql" alt="Portrait of David Liu" title="Portrait of David Liu" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/prime-editing-treats-childhood-brain-disease-mice" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=SoaktP-I 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ" alt="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" title="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Prime editing treats childhood brain disease in mice</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=QhzrPs_f 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single prime editing system could potentially treat multiple genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=m6KRxf-E 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ" alt="Susanna M. Hamilton, ӳ����ý Communications" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">More versatile and efficient base editor unlocks new gene-editing targets</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The authors tested two different base editors in mice — one called ABE8e and a modified version called ABE8e-V106W — and found that both efficiently corrected the <em>PEX1</em> mutation, but ABE8e-V106W was significantly better tolerated in the animals and made fewer off-target edits. When Kiran Musunuru of the University of Pennsylvania Perelman School of Medicine, one of baby KJ’s lead doctors, asked Liu which deaminase he and his team should use to correct KJ’s disease-causing mutation, Liu recommended ABE8e-V106W based on the data reported in today’s publication.</p> <p>“These observations, well before the data was published, suggested that ABE8e-V106W is an adenine base editor that sits in the Goldilocks zone, where it offers both high on-target activity that can efficiently correct a pathogenic mutation, and relatively low off-target activity that reduces the frequency of unwanted edits,” said <a target="_blank" href="/bios/david-liu">Liu</a>, Richard Merkin Professor, and director of the <a target="_blank" href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute for Transformative Technologies in Healthcare</a> at ӳ����ý the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>“It’s easy to assume that rescuing this quite-rare peroxisome disorder in mice wouldn’t have anything to do with saving a human baby with a very different life-threatening disease. But, it actually had a lot to do with it. It goes to show how science builds on itself, and how sharing the latest unpublished findings at a key moment can inform important decisions in the cutting-edge treatment of patients,” Liu added.</p> <p>The findings pave a path toward treating the root genetic cause of Zellweger spectrum disorder, a metabolic disease that affects about 1 in 50,000 to 90,000 births in North America.</p> <p>“Correcting the most common <em>PEX1</em> mutation is just the beginning of building meaningful treatment strategies for patients with Zellweger spectrum disorder, who currently have no options that treat the cause of the disease,” said lead author <a target="_blank" href="https://www.ophthalmology.pitt.edu/people/xin-daniel-gao-phd">Xin “Daniel” Gao</a>, now an Assistant Professor at the University of Pittsburgh, who led the project as a postdoctoral fellow in Liu’s lab. “More broadly, this work lays the foundation for using precision gene editing to develop better treatments for other rare peroxisomal diseases caused by mutations in PEX genes.”</p> <p>“A great deal of work went into the mouse modeling for this project. Ultimately, we developed a model that faithfully reproduces the disease and its long-chain fatty acid biomarkers, giving us strong confidence that these findings will translate into the clinic. This collaboration between David’s and my labs represents one of many joint efforts and serves as a cornerstone for future therapeutic advances emerging from the Center for Genetic Surgery,” said <a target="_blank" href="https://www.jax.org/research-and-faculty/faculty/research-scientists/cat-lutz">Lutz</a>, co-senior author of the study and vice president of the Rare Disease Translational Center at Jackson Laboratory.</p> <p><strong>Translational potential </strong> </p> <p>In their study, the researchers administered base editors to neonatal and older mice with the <em>PEX1</em> variant, using two adeno-associated viruses, which delivered the base editors to the livers of the animals. The team revealed that the base editor corrected the <em>PEX1</em> gene in roughly 60 percent of liver cells, high enough to restore peroxisome and liver function and lower the buildup of toxic metabolites throughout the body.</p> <p>The scientists also showed that the editing efficiency increased over the duration of the study — a lower dose of base editors was able to achieve the same level of editing over time as the higher dose the team tested.</p> <p>According to Liu, more research is needed to translate this work in mice into a potential treatment for humans. For example, the authors showed that the base editing system could be reformulated to be delivered using lipid nanoparticles, which have been used in several treatments for humans including KJ’s. However, further optimization of nanoparticle delivery of the base editor to treat Zellweger spectrum disorder (ZSD) remains to be done.</p> <p>One of Liu’s ultimate goals is to make personalized gene editing treatments accessible to patients on a broader scale through the new Center for Genetic Surgery (CGS) that he co-leads at ӳ����ý.</p> <p>“Currently, candidate CGS programs are ones for which a base or prime editor has been shown to correct a pathogenic mutation back to a healthy sequence, resulting in at least partial rescue of the disease in an animal model,” Liu said. “Demonstrating benefit to animals provides the foundation to move the study towards a clinical trial that we hope will eventually benefit patients with few treatment options.”</p> <p>“There is an urgent unmet need to develop and implement targeted therapies that address the root causes of thousands of genetic disorders. I am honored that our work on a common form of ZSD may have broader impact across other genetic diseases,” said <a target="_blank" href="https://keck.usc.edu/faculty-search/joseph-g-hacia/">Hacia</a>, co-senior author and medical geneticist at the Keck School of Medicine of University of Southern California. “Many children with ZSD develop life-threatening liver disease, leading to frequent hospitalizations and a shortened lifespan. We are driven by the hope of changing that reality and look forward to advancing this work into clinical trials to address liver disease in ZSD and related pathologies in other affected organs.”</p> <p>The study’s co-first authors are Xin “Daniel” Gao of ӳ����ý and Maximiliano Presa of Jackson Laboratory, and other co-authors include Nancy Braverman of McGill University and Guangping Gao of University of Massachusetts Chan Medical School.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health, the Global Foundation for Peroxisomal Disorders, and Wynne Mateffy Research Foundation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Gao XD, Presa M, et al. <a href="https://www.nature.com/articles/s41551-026-01651-5" target="_blank">In vivo base editing rescues liver pathophysiology and peroxisome dysfunction in a mouse model of Zellweger spectrum disorder</a>. <em>Nature Biomedical Engineering</em>. Online April 14, 2026. DOI: 10.1038/s41551-026-01651-5<br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/gene-editing" hreflang="en">Gene editing</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Mon, 10 Jun 2024 09:30:00 +0000 adicorat 5556946 at /news/scientists-generate-new-targeted-protein-degradation-system-tunes-cells-own-proteins <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" class="datetime">April 14, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The base editing enzyme used in this study is the same one that fixed Baby KJ Muldoon’s disease-causing mutation and saved his life in 2025.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" title="Tuesday, April 14, 2026 - 09:00" class="datetime">April 14, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A letter C is penciled into a long DNA sequence. "> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=x65fUlJp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=bcuAAMZD 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=WwHaTNVb 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy" alt="A letter C is penciled into a long DNA sequence. " title="A letter C is penciled into a long DNA sequence. " typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Susanna Hamilton </div> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/2196/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2196/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2196/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li data-list-item-id="e8d1325b084ac3c4798f4fe8846f1bfbc">Zellweger spectrum disorder is a group of genetic conditions that affect multiple organs in the body and the most severe form can be fatal in the first year of life.</li> <li aria-level="1" data-list-item-id="ee50c6be27935e16cc0c6f58877166496">Scientists used base editing to correct a disease-causing mutation in the <em>PEX1</em> gene in human cells and mice. This restored the function of peroxisomes, an organelle in the cell that malfunctions in these disorders.</li> <li aria-level="1" data-list-item-id="e345218bc482a038c22e0d62b5b42253a">The study, which began in 2020, guided the team to focus on a key base editor component — a deaminase enzyme — that was subsequently used to treat baby KJ Muldoon with a different genetic disease in 2025.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>In 2025, baby KJ Muldoon <a target="_blank" href="https://www.chop.edu/news/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital">became the first person</a> to receive a personalized gene editing treatment, which likely saved his life. But the scientific advances that made the groundbreaking treatment possible were years in the making long before KJ was born. One was base editing, the technology developed in 2016 by David Liu and his lab at the ӳ����ý that makes single-letter changes in DNA and was used to correct KJ’s life-threatening mutation.  </p> <p>Another advancement was the development and characterization of a specific version of a key base editor component: the enzyme called a deaminase, which converts a disease-causing DNA letter into a healthy one. Efforts to identify an optimal deaminase for a different genetic disorder began in 2020 in a collaboration between Liu’s lab and scientists from Jackson Laboratory and the University of Southern California (USC). The results of this project, published today in <a target="_blank" href="https://www.nature.com/articles/s41551-026-01651-5"><em>Nature Biomedical Engineering</em></a>, were so compelling that they spurred Liu to recommend using the same deaminase in <a target="_blank" href="https://www.nejm.org/doi/full/10.1056/NEJMoa2504747">KJ’s treatment</a> when the child’s doctors approached him in early 2025, even before the findings were published.</p> <p>In the new study, Liu and his team, in collaboration with scientists led by Cat Lutz at the Jackson Laboratory and Joe Hacia at USC, showed that base editing can correct mutations in the <em>PEX1</em> gene that cause Zellweger spectrum disorder , a rare, life-threatening condition that leads to liver and brain damage and is unrelated to KJ’s disease. The team demonstrated that this base edit, when made in a mouse model of the disorder, restored function of the liver and of peroxisomes — tiny fluid-filled sacs in cells that break down metabolic byproducts but are impaired as a result of the <em>PEX1</em> mutation. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Learn more</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Portrait of David Liu"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=glIu3Ovm 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql" alt="Portrait of David Liu" title="Portrait of David Liu" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/prime-editing-treats-childhood-brain-disease-mice" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=SoaktP-I 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ" alt="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" title="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Prime editing treats childhood brain disease in mice</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=QhzrPs_f 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single prime editing system could potentially treat multiple genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=m6KRxf-E 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ" alt="Susanna M. Hamilton, ӳ����ý Communications" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">More versatile and efficient base editor unlocks new gene-editing targets</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The authors tested two different base editors in mice — one called ABE8e and a modified version called ABE8e-V106W — and found that both efficiently corrected the <em>PEX1</em> mutation, but ABE8e-V106W was significantly better tolerated in the animals and made fewer off-target edits. When Kiran Musunuru of the University of Pennsylvania Perelman School of Medicine, one of baby KJ’s lead doctors, asked Liu which deaminase he and his team should use to correct KJ’s disease-causing mutation, Liu recommended ABE8e-V106W based on the data reported in today’s publication.</p> <p>“These observations, well before the data was published, suggested that ABE8e-V106W is an adenine base editor that sits in the Goldilocks zone, where it offers both high on-target activity that can efficiently correct a pathogenic mutation, and relatively low off-target activity that reduces the frequency of unwanted edits,” said <a target="_blank" href="/bios/david-liu">Liu</a>, Richard Merkin Professor, and director of the <a target="_blank" href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute for Transformative Technologies in Healthcare</a> at ӳ����ý the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>“It’s easy to assume that rescuing this quite-rare peroxisome disorder in mice wouldn’t have anything to do with saving a human baby with a very different life-threatening disease. But, it actually had a lot to do with it. It goes to show how science builds on itself, and how sharing the latest unpublished findings at a key moment can inform important decisions in the cutting-edge treatment of patients,” Liu added.</p> <p>The findings pave a path toward treating the root genetic cause of Zellweger spectrum disorder, a metabolic disease that affects about 1 in 50,000 to 90,000 births in North America.</p> <p>“Correcting the most common <em>PEX1</em> mutation is just the beginning of building meaningful treatment strategies for patients with Zellweger spectrum disorder, who currently have no options that treat the cause of the disease,” said lead author <a target="_blank" href="https://www.ophthalmology.pitt.edu/people/xin-daniel-gao-phd">Xin “Daniel” Gao</a>, now an Assistant Professor at the University of Pittsburgh, who led the project as a postdoctoral fellow in Liu’s lab. “More broadly, this work lays the foundation for using precision gene editing to develop better treatments for other rare peroxisomal diseases caused by mutations in PEX genes.”</p> <p>“A great deal of work went into the mouse modeling for this project. Ultimately, we developed a model that faithfully reproduces the disease and its long-chain fatty acid biomarkers, giving us strong confidence that these findings will translate into the clinic. This collaboration between David’s and my labs represents one of many joint efforts and serves as a cornerstone for future therapeutic advances emerging from the Center for Genetic Surgery,” said <a target="_blank" href="https://www.jax.org/research-and-faculty/faculty/research-scientists/cat-lutz">Lutz</a>, co-senior author of the study and vice president of the Rare Disease Translational Center at Jackson Laboratory.</p> <p><strong>Translational potential </strong> </p> <p>In their study, the researchers administered base editors to neonatal and older mice with the <em>PEX1</em> variant, using two adeno-associated viruses, which delivered the base editors to the livers of the animals. The team revealed that the base editor corrected the <em>PEX1</em> gene in roughly 60 percent of liver cells, high enough to restore peroxisome and liver function and lower the buildup of toxic metabolites throughout the body.</p> <p>The scientists also showed that the editing efficiency increased over the duration of the study — a lower dose of base editors was able to achieve the same level of editing over time as the higher dose the team tested.</p> <p>According to Liu, more research is needed to translate this work in mice into a potential treatment for humans. For example, the authors showed that the base editing system could be reformulated to be delivered using lipid nanoparticles, which have been used in several treatments for humans including KJ’s. However, further optimization of nanoparticle delivery of the base editor to treat Zellweger spectrum disorder (ZSD) remains to be done.</p> <p>One of Liu’s ultimate goals is to make personalized gene editing treatments accessible to patients on a broader scale through the new Center for Genetic Surgery (CGS) that he co-leads at ӳ����ý.</p> <p>“Currently, candidate CGS programs are ones for which a base or prime editor has been shown to correct a pathogenic mutation back to a healthy sequence, resulting in at least partial rescue of the disease in an animal model,” Liu said. “Demonstrating benefit to animals provides the foundation to move the study towards a clinical trial that we hope will eventually benefit patients with few treatment options.”</p> <p>“There is an urgent unmet need to develop and implement targeted therapies that address the root causes of thousands of genetic disorders. I am honored that our work on a common form of ZSD may have broader impact across other genetic diseases,” said <a target="_blank" href="https://keck.usc.edu/faculty-search/joseph-g-hacia/">Hacia</a>, co-senior author and medical geneticist at the Keck School of Medicine of University of Southern California. “Many children with ZSD develop life-threatening liver disease, leading to frequent hospitalizations and a shortened lifespan. We are driven by the hope of changing that reality and look forward to advancing this work into clinical trials to address liver disease in ZSD and related pathologies in other affected organs.”</p> <p>The study’s co-first authors are Xin “Daniel” Gao of ӳ����ý and Maximiliano Presa of Jackson Laboratory, and other co-authors include Nancy Braverman of McGill University and Guangping Gao of University of Massachusetts Chan Medical School.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health, the Global Foundation for Peroxisomal Disorders, and Wynne Mateffy Research Foundation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Gao XD, Presa M, et al. <a href="https://www.nature.com/articles/s41551-026-01651-5" target="_blank">In vivo base editing rescues liver pathophysiology and peroxisome dysfunction in a mouse model of Zellweger spectrum disorder</a>. <em>Nature Biomedical Engineering</em>. Online April 14, 2026. DOI: 10.1038/s41551-026-01651-5<br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/gene-editing" hreflang="en">Gene editing</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Thu, 14 Mar 2024 19:29:06 +0000 leah@broadinstitute.org 5556676 at /news/researchers-engineer-vivo-delivery-system-prime-editing-partially-restoring-vision-mice <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" class="datetime">April 14, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The base editing enzyme used in this study is the same one that fixed Baby KJ Muldoon’s disease-causing mutation and saved his life in 2025.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" title="Tuesday, April 14, 2026 - 09:00" class="datetime">April 14, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A letter C is penciled into a long DNA sequence. "> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=x65fUlJp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=bcuAAMZD 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=WwHaTNVb 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy" alt="A letter C is penciled into a long DNA sequence. " title="A letter C is penciled into a long DNA sequence. " typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Susanna Hamilton </div> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/2196/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2196/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2196/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li data-list-item-id="e8d1325b084ac3c4798f4fe8846f1bfbc">Zellweger spectrum disorder is a group of genetic conditions that affect multiple organs in the body and the most severe form can be fatal in the first year of life.</li> <li aria-level="1" data-list-item-id="ee50c6be27935e16cc0c6f58877166496">Scientists used base editing to correct a disease-causing mutation in the <em>PEX1</em> gene in human cells and mice. This restored the function of peroxisomes, an organelle in the cell that malfunctions in these disorders.</li> <li aria-level="1" data-list-item-id="e345218bc482a038c22e0d62b5b42253a">The study, which began in 2020, guided the team to focus on a key base editor component — a deaminase enzyme — that was subsequently used to treat baby KJ Muldoon with a different genetic disease in 2025.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>In 2025, baby KJ Muldoon <a target="_blank" href="https://www.chop.edu/news/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital">became the first person</a> to receive a personalized gene editing treatment, which likely saved his life. But the scientific advances that made the groundbreaking treatment possible were years in the making long before KJ was born. One was base editing, the technology developed in 2016 by David Liu and his lab at the ӳ����ý that makes single-letter changes in DNA and was used to correct KJ’s life-threatening mutation.  </p> <p>Another advancement was the development and characterization of a specific version of a key base editor component: the enzyme called a deaminase, which converts a disease-causing DNA letter into a healthy one. Efforts to identify an optimal deaminase for a different genetic disorder began in 2020 in a collaboration between Liu’s lab and scientists from Jackson Laboratory and the University of Southern California (USC). The results of this project, published today in <a target="_blank" href="https://www.nature.com/articles/s41551-026-01651-5"><em>Nature Biomedical Engineering</em></a>, were so compelling that they spurred Liu to recommend using the same deaminase in <a target="_blank" href="https://www.nejm.org/doi/full/10.1056/NEJMoa2504747">KJ’s treatment</a> when the child’s doctors approached him in early 2025, even before the findings were published.</p> <p>In the new study, Liu and his team, in collaboration with scientists led by Cat Lutz at the Jackson Laboratory and Joe Hacia at USC, showed that base editing can correct mutations in the <em>PEX1</em> gene that cause Zellweger spectrum disorder , a rare, life-threatening condition that leads to liver and brain damage and is unrelated to KJ’s disease. The team demonstrated that this base edit, when made in a mouse model of the disorder, restored function of the liver and of peroxisomes — tiny fluid-filled sacs in cells that break down metabolic byproducts but are impaired as a result of the <em>PEX1</em> mutation. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Learn more</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Portrait of David Liu"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=glIu3Ovm 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql" alt="Portrait of David Liu" title="Portrait of David Liu" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/prime-editing-treats-childhood-brain-disease-mice" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=SoaktP-I 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ" alt="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" title="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Prime editing treats childhood brain disease in mice</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=QhzrPs_f 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single prime editing system could potentially treat multiple genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=m6KRxf-E 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ" alt="Susanna M. Hamilton, ӳ����ý Communications" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">More versatile and efficient base editor unlocks new gene-editing targets</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The authors tested two different base editors in mice — one called ABE8e and a modified version called ABE8e-V106W — and found that both efficiently corrected the <em>PEX1</em> mutation, but ABE8e-V106W was significantly better tolerated in the animals and made fewer off-target edits. When Kiran Musunuru of the University of Pennsylvania Perelman School of Medicine, one of baby KJ’s lead doctors, asked Liu which deaminase he and his team should use to correct KJ’s disease-causing mutation, Liu recommended ABE8e-V106W based on the data reported in today’s publication.</p> <p>“These observations, well before the data was published, suggested that ABE8e-V106W is an adenine base editor that sits in the Goldilocks zone, where it offers both high on-target activity that can efficiently correct a pathogenic mutation, and relatively low off-target activity that reduces the frequency of unwanted edits,” said <a target="_blank" href="/bios/david-liu">Liu</a>, Richard Merkin Professor, and director of the <a target="_blank" href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute for Transformative Technologies in Healthcare</a> at ӳ����ý the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>“It’s easy to assume that rescuing this quite-rare peroxisome disorder in mice wouldn’t have anything to do with saving a human baby with a very different life-threatening disease. But, it actually had a lot to do with it. It goes to show how science builds on itself, and how sharing the latest unpublished findings at a key moment can inform important decisions in the cutting-edge treatment of patients,” Liu added.</p> <p>The findings pave a path toward treating the root genetic cause of Zellweger spectrum disorder, a metabolic disease that affects about 1 in 50,000 to 90,000 births in North America.</p> <p>“Correcting the most common <em>PEX1</em> mutation is just the beginning of building meaningful treatment strategies for patients with Zellweger spectrum disorder, who currently have no options that treat the cause of the disease,” said lead author <a target="_blank" href="https://www.ophthalmology.pitt.edu/people/xin-daniel-gao-phd">Xin “Daniel” Gao</a>, now an Assistant Professor at the University of Pittsburgh, who led the project as a postdoctoral fellow in Liu’s lab. “More broadly, this work lays the foundation for using precision gene editing to develop better treatments for other rare peroxisomal diseases caused by mutations in PEX genes.”</p> <p>“A great deal of work went into the mouse modeling for this project. Ultimately, we developed a model that faithfully reproduces the disease and its long-chain fatty acid biomarkers, giving us strong confidence that these findings will translate into the clinic. This collaboration between David’s and my labs represents one of many joint efforts and serves as a cornerstone for future therapeutic advances emerging from the Center for Genetic Surgery,” said <a target="_blank" href="https://www.jax.org/research-and-faculty/faculty/research-scientists/cat-lutz">Lutz</a>, co-senior author of the study and vice president of the Rare Disease Translational Center at Jackson Laboratory.</p> <p><strong>Translational potential </strong> </p> <p>In their study, the researchers administered base editors to neonatal and older mice with the <em>PEX1</em> variant, using two adeno-associated viruses, which delivered the base editors to the livers of the animals. The team revealed that the base editor corrected the <em>PEX1</em> gene in roughly 60 percent of liver cells, high enough to restore peroxisome and liver function and lower the buildup of toxic metabolites throughout the body.</p> <p>The scientists also showed that the editing efficiency increased over the duration of the study — a lower dose of base editors was able to achieve the same level of editing over time as the higher dose the team tested.</p> <p>According to Liu, more research is needed to translate this work in mice into a potential treatment for humans. For example, the authors showed that the base editing system could be reformulated to be delivered using lipid nanoparticles, which have been used in several treatments for humans including KJ’s. However, further optimization of nanoparticle delivery of the base editor to treat Zellweger spectrum disorder (ZSD) remains to be done.</p> <p>One of Liu’s ultimate goals is to make personalized gene editing treatments accessible to patients on a broader scale through the new Center for Genetic Surgery (CGS) that he co-leads at ӳ����ý.</p> <p>“Currently, candidate CGS programs are ones for which a base or prime editor has been shown to correct a pathogenic mutation back to a healthy sequence, resulting in at least partial rescue of the disease in an animal model,” Liu said. “Demonstrating benefit to animals provides the foundation to move the study towards a clinical trial that we hope will eventually benefit patients with few treatment options.”</p> <p>“There is an urgent unmet need to develop and implement targeted therapies that address the root causes of thousands of genetic disorders. I am honored that our work on a common form of ZSD may have broader impact across other genetic diseases,” said <a target="_blank" href="https://keck.usc.edu/faculty-search/joseph-g-hacia/">Hacia</a>, co-senior author and medical geneticist at the Keck School of Medicine of University of Southern California. “Many children with ZSD develop life-threatening liver disease, leading to frequent hospitalizations and a shortened lifespan. We are driven by the hope of changing that reality and look forward to advancing this work into clinical trials to address liver disease in ZSD and related pathologies in other affected organs.”</p> <p>The study’s co-first authors are Xin “Daniel” Gao of ӳ����ý and Maximiliano Presa of Jackson Laboratory, and other co-authors include Nancy Braverman of McGill University and Guangping Gao of University of Massachusetts Chan Medical School.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health, the Global Foundation for Peroxisomal Disorders, and Wynne Mateffy Research Foundation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Gao XD, Presa M, et al. <a href="https://www.nature.com/articles/s41551-026-01651-5" target="_blank">In vivo base editing rescues liver pathophysiology and peroxisome dysfunction in a mouse model of Zellweger spectrum disorder</a>. <em>Nature Biomedical Engineering</em>. Online April 14, 2026. DOI: 10.1038/s41551-026-01651-5<br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/gene-editing" hreflang="en">Gene editing</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Mon, 08 Jan 2024 11:29:17 +0000 Corie Lok 5556226 at /news/prime-editing-shows-proof-concept-treating-sickle-cell-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Jessica Colarossi</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" class="datetime">April 14, 2026</time> </span> <div class="hero-section container"> <div class="hero-section__row row"> <div class="hero-section__content hero-section__content_left col-6"> <div class="hero-section__breadcrumbs"> <div class="block block-system block-system-breadcrumb-block"> <nav class="breadcrumb" role="navigation" aria-labelledby="system-breadcrumb"> <h2 id="system-breadcrumb" class="visually-hidden">Breadcrumb</h2> <ol> <li> <a href="/">Home</a> </li> <li> <a href="/news">News</a> </li> </ol> </nav> </div> </div> <div class="hero-section__title"> <div class="block block-layout-builder block-field-blocknodelong-storytitle"> <span class="field field--name-title field--type-string field--label-hidden"><h1>Base editing repairs mutation and liver function in mouse model of Zellweger spectrum disorder</h1> </span> </div> </div> <div class="hero-section__description"> <div class="block block-layout-builder block-field-blocknodelong-storybody"> <div class="clearfix text-formatted field field--name-body field--type-text-with-summary field--label-hidden field__item"><p>The base editing enzyme used in this study is the same one that fixed Baby KJ Muldoon’s disease-causing mutation and saved his life in 2025.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Jessica Colarossi </div> </div> <div class="hero-section__date"> <div class="block block-layout-builder block-field-blocknodelong-storycreated"> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2026-04-14T09:00:00-04:00" title="Tuesday, April 14, 2026 - 09:00" class="datetime">April 14, 2026</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A letter C is penciled into a long DNA sequence. "> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=DoQDC_zP 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=x65fUlJp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=bcuAAMZD 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=WwHaTNVb 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/News_base-editing-Liu_ext-main_040826.png?itok=vzoo2VYy" alt="A letter C is penciled into a long DNA sequence. " title="A letter C is penciled into a long DNA sequence. " typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Susanna Hamilton </div> <div class="media-caption__description"> </div> </div> </article> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block block-better-social-sharing-buttons block-social-sharing-buttons-block"> <div style="display: none"><link rel="preload" href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg" as="image" type="image/svg+xml" crossorigin="anonymous" /></div> <div class="social-sharing-buttons"> <a href="https://www.facebook.com/sharer/sharer.php?u=/taxonomy/term/2196/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2196/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2196/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="background-color:#f3f3f3;font-family:Open Sans;margin-bottom:2em;padding:2em;"> <h3>Highlights</h3> <ul> <li data-list-item-id="e8d1325b084ac3c4798f4fe8846f1bfbc">Zellweger spectrum disorder is a group of genetic conditions that affect multiple organs in the body and the most severe form can be fatal in the first year of life.</li> <li aria-level="1" data-list-item-id="ee50c6be27935e16cc0c6f58877166496">Scientists used base editing to correct a disease-causing mutation in the <em>PEX1</em> gene in human cells and mice. This restored the function of peroxisomes, an organelle in the cell that malfunctions in these disorders.</li> <li aria-level="1" data-list-item-id="e345218bc482a038c22e0d62b5b42253a">The study, which began in 2020, guided the team to focus on a key base editor component — a deaminase enzyme — that was subsequently used to treat baby KJ Muldoon with a different genetic disease in 2025.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>In 2025, baby KJ Muldoon <a target="_blank" href="https://www.chop.edu/news/worlds-first-patient-treated-personalized-crispr-gene-editing-therapy-childrens-hospital">became the first person</a> to receive a personalized gene editing treatment, which likely saved his life. But the scientific advances that made the groundbreaking treatment possible were years in the making long before KJ was born. One was base editing, the technology developed in 2016 by David Liu and his lab at the ӳ����ý that makes single-letter changes in DNA and was used to correct KJ’s life-threatening mutation.  </p> <p>Another advancement was the development and characterization of a specific version of a key base editor component: the enzyme called a deaminase, which converts a disease-causing DNA letter into a healthy one. Efforts to identify an optimal deaminase for a different genetic disorder began in 2020 in a collaboration between Liu’s lab and scientists from Jackson Laboratory and the University of Southern California (USC). The results of this project, published today in <a target="_blank" href="https://www.nature.com/articles/s41551-026-01651-5"><em>Nature Biomedical Engineering</em></a>, were so compelling that they spurred Liu to recommend using the same deaminase in <a target="_blank" href="https://www.nejm.org/doi/full/10.1056/NEJMoa2504747">KJ’s treatment</a> when the child’s doctors approached him in early 2025, even before the findings were published.</p> <p>In the new study, Liu and his team, in collaboration with scientists led by Cat Lutz at the Jackson Laboratory and Joe Hacia at USC, showed that base editing can correct mutations in the <em>PEX1</em> gene that cause Zellweger spectrum disorder , a rare, life-threatening condition that leads to liver and brain damage and is unrelated to KJ’s disease. The team demonstrated that this base edit, when made in a mouse model of the disorder, restored function of the liver and of peroxisomes — tiny fluid-filled sacs in cells that break down metabolic byproducts but are impaired as a result of the <em>PEX1</em> mutation. </p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Learn more</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Portrait of David Liu"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=qAIk-tPD 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=ULIU8jAb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=glIu3Ovm 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/DavidLiu_CaseyAtkins_1_mo-BROAD00254719.jpg?h=3dc33712&itok=zC3ZKeql" alt="Portrait of David Liu" title="Portrait of David Liu" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/prime-editing-treats-childhood-brain-disease-mice" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=wehH4Ame 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=S3l31d6N 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=SoaktP-I 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=rwHlkGIZ" alt="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" title="Microscopy image showing human neurons in blue (indicating cell nuclei) and green (indicating mutated protein)" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/prime-editing-treats-childhood-brain-disease-mice" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Prime editing treats childhood brain disease in mice</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1921px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=P1HVVzXL 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=KdKAIdzp 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=QhzrPs_f 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=3LTrPTP3" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Single prime editing system could potentially treat multiple genetic diseases</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture role="img" aria-label> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=XUjeM0-G 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=OhnM3prb 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=m6KRxf-E 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets"><img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2020/Base_editing.jpg?h=d3e04ee7&itok=0xlEqtwJ" alt="Susanna M. Hamilton, ӳ����ý Communications" typeof="foaf:Image"></a> </picture> </div> </article> </div> <div class="node__content"> <a href="/news/more-versatile-and-efficient-base-editor-unlocks-new-gene-editing-targets" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">More versatile and efficient base editor unlocks new gene-editing targets</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The authors tested two different base editors in mice — one called ABE8e and a modified version called ABE8e-V106W — and found that both efficiently corrected the <em>PEX1</em> mutation, but ABE8e-V106W was significantly better tolerated in the animals and made fewer off-target edits. When Kiran Musunuru of the University of Pennsylvania Perelman School of Medicine, one of baby KJ’s lead doctors, asked Liu which deaminase he and his team should use to correct KJ’s disease-causing mutation, Liu recommended ABE8e-V106W based on the data reported in today’s publication.</p> <p>“These observations, well before the data was published, suggested that ABE8e-V106W is an adenine base editor that sits in the Goldilocks zone, where it offers both high on-target activity that can efficiently correct a pathogenic mutation, and relatively low off-target activity that reduces the frequency of unwanted edits,” said <a target="_blank" href="/bios/david-liu">Liu</a>, Richard Merkin Professor, and director of the <a target="_blank" href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute for Transformative Technologies in Healthcare</a> at ӳ����ý the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>“It’s easy to assume that rescuing this quite-rare peroxisome disorder in mice wouldn’t have anything to do with saving a human baby with a very different life-threatening disease. But, it actually had a lot to do with it. It goes to show how science builds on itself, and how sharing the latest unpublished findings at a key moment can inform important decisions in the cutting-edge treatment of patients,” Liu added.</p> <p>The findings pave a path toward treating the root genetic cause of Zellweger spectrum disorder, a metabolic disease that affects about 1 in 50,000 to 90,000 births in North America.</p> <p>“Correcting the most common <em>PEX1</em> mutation is just the beginning of building meaningful treatment strategies for patients with Zellweger spectrum disorder, who currently have no options that treat the cause of the disease,” said lead author <a target="_blank" href="https://www.ophthalmology.pitt.edu/people/xin-daniel-gao-phd">Xin “Daniel” Gao</a>, now an Assistant Professor at the University of Pittsburgh, who led the project as a postdoctoral fellow in Liu’s lab. “More broadly, this work lays the foundation for using precision gene editing to develop better treatments for other rare peroxisomal diseases caused by mutations in PEX genes.”</p> <p>“A great deal of work went into the mouse modeling for this project. Ultimately, we developed a model that faithfully reproduces the disease and its long-chain fatty acid biomarkers, giving us strong confidence that these findings will translate into the clinic. This collaboration between David’s and my labs represents one of many joint efforts and serves as a cornerstone for future therapeutic advances emerging from the Center for Genetic Surgery,” said <a target="_blank" href="https://www.jax.org/research-and-faculty/faculty/research-scientists/cat-lutz">Lutz</a>, co-senior author of the study and vice president of the Rare Disease Translational Center at Jackson Laboratory.</p> <p><strong>Translational potential </strong> </p> <p>In their study, the researchers administered base editors to neonatal and older mice with the <em>PEX1</em> variant, using two adeno-associated viruses, which delivered the base editors to the livers of the animals. The team revealed that the base editor corrected the <em>PEX1</em> gene in roughly 60 percent of liver cells, high enough to restore peroxisome and liver function and lower the buildup of toxic metabolites throughout the body.</p> <p>The scientists also showed that the editing efficiency increased over the duration of the study — a lower dose of base editors was able to achieve the same level of editing over time as the higher dose the team tested.</p> <p>According to Liu, more research is needed to translate this work in mice into a potential treatment for humans. For example, the authors showed that the base editing system could be reformulated to be delivered using lipid nanoparticles, which have been used in several treatments for humans including KJ’s. However, further optimization of nanoparticle delivery of the base editor to treat Zellweger spectrum disorder (ZSD) remains to be done.</p> <p>One of Liu’s ultimate goals is to make personalized gene editing treatments accessible to patients on a broader scale through the new Center for Genetic Surgery (CGS) that he co-leads at ӳ����ý.</p> <p>“Currently, candidate CGS programs are ones for which a base or prime editor has been shown to correct a pathogenic mutation back to a healthy sequence, resulting in at least partial rescue of the disease in an animal model,” Liu said. “Demonstrating benefit to animals provides the foundation to move the study towards a clinical trial that we hope will eventually benefit patients with few treatment options.”</p> <p>“There is an urgent unmet need to develop and implement targeted therapies that address the root causes of thousands of genetic disorders. I am honored that our work on a common form of ZSD may have broader impact across other genetic diseases,” said <a target="_blank" href="https://keck.usc.edu/faculty-search/joseph-g-hacia/">Hacia</a>, co-senior author and medical geneticist at the Keck School of Medicine of University of Southern California. “Many children with ZSD develop life-threatening liver disease, leading to frequent hospitalizations and a shortened lifespan. We are driven by the hope of changing that reality and look forward to advancing this work into clinical trials to address liver disease in ZSD and related pathologies in other affected organs.”</p> <p>The study’s co-first authors are Xin “Daniel” Gao of ӳ����ý and Maximiliano Presa of Jackson Laboratory, and other co-authors include Nancy Braverman of McGill University and Guangping Gao of University of Massachusetts Chan Medical School.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro paragraph--view-mode--default"> <div class="field field--name-field-paragraph field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This work was supported by the National Institutes of Health, the Global Foundation for Peroxisomal Disorders, and Wynne Mateffy Research Foundation.</p> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--table-outro-row paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Gao XD, Presa M, et al. <a href="https://www.nature.com/articles/s41551-026-01651-5" target="_blank">In vivo base editing rescues liver pathophysiology and peroxisome dysfunction in a mouse model of Zellweger spectrum disorder</a>. <em>Nature Biomedical Engineering</em>. Online April 14, 2026. DOI: 10.1038/s41551-026-01651-5<br> </p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/gene-editing" hreflang="en">Gene editing</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Mon, 17 Apr 2023 15:53:54 +0000 kzusi@broadinstitute.org 1282061 at