Rare Disease / en Mon, 21 Jul 25 11:37:05 -0400 Prime editing treats childhood brain disease in mice /news/prime-editing-treats-childhood-brain-disease-mice <span class="field field--name-title field--type-string field--label-hidden"><h1>Prime editing treats childhood brain disease in mice</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Corie Lok</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-07-21T11:37:05-04:00" class="datetime">July 21, 2025</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>Prime editing treats childhood brain disease in mice</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>Scientists use a precise form of gene editing called prime editing to correct the most common genetic mutations that cause alternating hemiplegia of childhood, a rare and severe neurological disorder that begins in infancy.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Sarah C.P. Williams </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="2025-07-21T11:37:05-04:00" title="Monday, July 21, 2025 - 11:37" class="datetime">July 21, 2025</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> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=4v-1bgTe 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=vcca1mnQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=EgQptYlI 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9" 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" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Kathleen Sweadner, Christine Simmons, and Alfred George </div> <div class="media-caption__description"> Scientists studied cultured human neurons, shown here under a microscope, that have a protein (green) with a mutation that causes alternating hemiplegia of childhood. </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/619/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 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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-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>Related news</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/prime-editing-efficiently-corrects-cystic-fibrosis-mutation-human-lung-cells" class="node"> <div class="field field--name-field-image 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system inserts entire genes in human cells</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" 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"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=ffrhaQKJ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj" alt="Susanna Hamilton, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Next generation prime editing systems move closer to possible therapeutic applications</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>By the time they are a few months old, infants born with alternating hemiplegia of childhood (AHC) begin experiencing terrifying episodes of paralysis and seizures, and will soon show developmental delays and intellectual disability. There is no cure or effective treatment for this rare genetic disease, but new research suggests a potential path to one. </p> <p>Researchers at the ӳý and The Jackson Laboratory have used prime editing, a precise and versatile form of gene editing, to correct the root cause of AHC in mice. The team used a scalable approach to develop prime editing treatments that directly repaired five different AHC-causing genetic mutations. Mice that received the treatment had far fewer and less severe symptoms of AHC, and survived more than twice as long as untreated mice. </p> <p>The new study, published in <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank"><em>Cell</em></a>, is the first time prime editing has been used to treat a neurological disease in animals, offering hope for treating people with AHC and other genetic brain disorders. <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">Prime editing was developed in 2019</a> by the lab of <a href="/bios/david-liu">David Liu</a>, a ӳý core institute member and co-senior author of the new paper. The technology has already been successfully tested in a clinical trial for another rare genetic disease.</p> <p>“This study is an important milestone for prime editing and one of the most exciting examples of therapeutic gene editing to come from our team,” said Liu, Richard Merkin Professor and director of the <a href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute of Transformative Technologies in Healthcare at the ӳý</a>. “It opens the door to one day repairing the underlying genetic causes of many neurological disorders that have long been considered untreatable.” Liu is also a Howard Hughes Medical Institute investigator and a professor at Harvard University.</p> <p>The ability to precisely edit DNA directly in the brain has important implications for neurological diseases, said Cathleen Lutz, vice president of the Rare Disease Translational Center at The Jackson Laboratory and co-senior author of the study. “This level of editing efficiency in the brain is really quite remarkable.”</p> <p>The team’s patient partner is RARE Hope (formerly Hope for Annabel), a non-profit focused on accelerating research on AHC and developing scalable, patient-centric research platforms to benefit the larger rare disease community. RARE Hope initiated the collaboration and was closely engaged throughout the project. </p> <p>“This study is a win not just for our community but for all rare neurological conditions, and a breakthrough moment in expanding access to a broader cohort of potential patients,” said Nina Frost, founder and president of RARE Hope, a co-author of the study, and mother of a daughter with AHC. “It’s been a privilege to collaborate on such a scientifically significant effort with a team that has kept patients at the center of proof-of-concept research — engaging the patient community, modeling the patient experience, and integrating patient priorities into experimental design. This is a model for patient-relevant, patient-centered research because the team included us as true partners.”</p> <h2>Brain gene editing</h2> <p>The vast majority of AHC cases are caused by one of four mutations in <em>ATP1A3</em>, a gene essential for brain cell function. In the new work, Liu’s team set out to simultaneously develop prime editing treatments that could fix five <em>ATP1A3 </em>mutations, including the four most common — a scale rarely attempted in therapeutic gene editing research. Most other gene editing treatments, such as <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic">one recently used to treat baby KJ Muldoon</a>, are designed to correct one mutation at a time. The scientists worked on correcting all five mutations, streamlining experiments, saving resources, and testing the robustness of the underlying science.</p> <p>“We developed a robust framework to correct multiple mutations in parallel,” said Alexander Sousa, a postdoctoral fellow in the Liu lab and one of three co-first authors along with Holt Sakai of the Liu lab and Markus Terrey of The Jackson Laboratory. “This effort was really about creating a blueprint that could be rapidly applied to other rare diseases too.”</p> <p>The researchers first tested their strategies in cultured cells from patients with AHC. They demonstrated that they could correctly repair AHC mutations in up to 90 percent of treated cells, with minimal changes to other stretches of DNA. </p> <p>Next, the group collaborated with Jackson Lab researchers to test their treatments in two mouse models of AHC, which carry <em>Atp1a3 </em>mutations similar to those in patients with AHC. Without treatment, the mice developed seizures, movement problems, and died prematurely. When the scientists injected their editing system into the brains of the animals, their symptoms disappeared or were substantially reduced. Treated mice survived more than twice as long as untreated animals. Moreover, the function of their Atp1a3 protein was restored in the brain, and their motor and cognitive deficits were ameliorated. The scientists delivered the prime editors to cells in mice using clinically validated viruses called AAVs, which are already used in FDA-approved gene therapies targeting brain cells.</p> <p>“The results really exceeded our expectations,” said Sakai. “It was incredibly exciting to see that data.”</p> <p>The team also tested traditional gene therapy, which delivered an extra, healthy copy of the <em>ATP1A3 </em>gene to cells, and found that symptoms did not improve in animals. This finding highlights the unique advantage of using gene editing to directly correct a mutation that results in a malfunctioning, disease-causing protein, the researchers said. </p> <p>“Before this study, we didn’t even know if we could intervene in AHC after birth in an animal,” said Sousa. “Now we know you can.”</p> <h2>A template for rare diseases</h2> <p>Because the treatment required direct injection into the brain shortly after birth, the team is now exploring less invasive delivery methods, and whether treatment later in life could still be effective. </p> <p>Beyond AHC, the team sees their approach as a template for tackling other rare genetic diseases — especially those that affect the brain. With the ability to rapidly design and test multiple gene editing treatments at once, they hope to bring the same precision and speed to many other conditions.</p> <p>“This is a powerful proof of concept,” said Sakai. “It shows that we can use prime editing to treat genetic brain diseases, and it lays the groundwork for translating this approach to the clinic.”<br>  </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>Support for the study was provided by the National Institutes of Health, the Chan-Zuckerberg Initiative, RARE Hope, the Alternating Hemiplegia of Childhood Foundation, the For Henry AHC Foundation, the Davis Family Foundation, the Toolbox Foundation L2C Initiative, the Cure AHC Foundation, the Howard Hughes Medical Institute, and the National Science 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>Sousa AA, Terrey M, Sakai HA et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank">In vivo prime editing rescues alternating hemiplegia of childhood in mice</a>. <em>Cell</em>. Online July 21, 2025. DOI: 10.1016/j.cell.2025.06.038</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/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 Count Me In launches new patient-partnered research project for translocation renal cell carcinoma /news/count-me-launches-new-patient-partnered-research-project-translocation-renal-cell-carcinoma <span class="field field--name-title field--type-string field--label-hidden"><h1>Prime editing treats childhood brain disease in mice</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Corie Lok</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-07-21T11:37:05-04:00" class="datetime">July 21, 2025</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>Prime editing treats childhood brain disease in mice</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>Scientists use a precise form of gene editing called prime editing to correct the most common genetic mutations that cause alternating hemiplegia of childhood, a rare and severe neurological disorder that begins in infancy.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Sarah C.P. Williams </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="2025-07-21T11:37:05-04:00" title="Monday, July 21, 2025 - 11:37" class="datetime">July 21, 2025</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> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=4v-1bgTe 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=vcca1mnQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=EgQptYlI 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9" 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" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Kathleen Sweadner, Christine Simmons, and Alfred George </div> <div class="media-caption__description"> Scientists studied cultured human neurons, shown here under a microscope, that have a protein (green) with a mutation that causes alternating hemiplegia of childhood. </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/619/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 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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-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>Related news</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/prime-editing-efficiently-corrects-cystic-fibrosis-mutation-human-lung-cells" class="node"> <div class="field field--name-field-image 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in railroad tracks that are colored like DNA." title="Graphic displaying a green protein filling a gap in railroad tracks that are colored like DNA." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/improved-prime-editing-system-makes-gene-sized-edits-human-cells-therapeutic-levels" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Improved prime editing system makes gene-sized edits in human cells at therapeutic levels</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/new-prime-editing-system-inserts-entire-genes-human-cells" 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"> <a href="/news/new-prime-editing-system-inserts-entire-genes-human-cells"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/TwinPE-07.jpg?h=9423a5c0&itok=hCpTpO4i 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=hCpTpO4i 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=JBB_oOB9 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=JBB_oOB9 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=XOGiyqIC 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=l-wsLX11 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/TwinPE-07.jpg?h=9423a5c0&itok=l-wsLX11" alt="Ricardo Job-Reese, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/new-prime-editing-system-inserts-entire-genes-human-cells" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">New prime editing system inserts entire genes in human cells</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" 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"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=ffrhaQKJ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj" alt="Susanna Hamilton, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Next generation prime editing systems move closer to possible therapeutic applications</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>By the time they are a few months old, infants born with alternating hemiplegia of childhood (AHC) begin experiencing terrifying episodes of paralysis and seizures, and will soon show developmental delays and intellectual disability. There is no cure or effective treatment for this rare genetic disease, but new research suggests a potential path to one. </p> <p>Researchers at the ӳý and The Jackson Laboratory have used prime editing, a precise and versatile form of gene editing, to correct the root cause of AHC in mice. The team used a scalable approach to develop prime editing treatments that directly repaired five different AHC-causing genetic mutations. Mice that received the treatment had far fewer and less severe symptoms of AHC, and survived more than twice as long as untreated mice. </p> <p>The new study, published in <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank"><em>Cell</em></a>, is the first time prime editing has been used to treat a neurological disease in animals, offering hope for treating people with AHC and other genetic brain disorders. <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">Prime editing was developed in 2019</a> by the lab of <a href="/bios/david-liu">David Liu</a>, a ӳý core institute member and co-senior author of the new paper. The technology has already been successfully tested in a clinical trial for another rare genetic disease.</p> <p>“This study is an important milestone for prime editing and one of the most exciting examples of therapeutic gene editing to come from our team,” said Liu, Richard Merkin Professor and director of the <a href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute of Transformative Technologies in Healthcare at the ӳý</a>. “It opens the door to one day repairing the underlying genetic causes of many neurological disorders that have long been considered untreatable.” Liu is also a Howard Hughes Medical Institute investigator and a professor at Harvard University.</p> <p>The ability to precisely edit DNA directly in the brain has important implications for neurological diseases, said Cathleen Lutz, vice president of the Rare Disease Translational Center at The Jackson Laboratory and co-senior author of the study. “This level of editing efficiency in the brain is really quite remarkable.”</p> <p>The team’s patient partner is RARE Hope (formerly Hope for Annabel), a non-profit focused on accelerating research on AHC and developing scalable, patient-centric research platforms to benefit the larger rare disease community. RARE Hope initiated the collaboration and was closely engaged throughout the project. </p> <p>“This study is a win not just for our community but for all rare neurological conditions, and a breakthrough moment in expanding access to a broader cohort of potential patients,” said Nina Frost, founder and president of RARE Hope, a co-author of the study, and mother of a daughter with AHC. “It’s been a privilege to collaborate on such a scientifically significant effort with a team that has kept patients at the center of proof-of-concept research — engaging the patient community, modeling the patient experience, and integrating patient priorities into experimental design. This is a model for patient-relevant, patient-centered research because the team included us as true partners.”</p> <h2>Brain gene editing</h2> <p>The vast majority of AHC cases are caused by one of four mutations in <em>ATP1A3</em>, a gene essential for brain cell function. In the new work, Liu’s team set out to simultaneously develop prime editing treatments that could fix five <em>ATP1A3 </em>mutations, including the four most common — a scale rarely attempted in therapeutic gene editing research. Most other gene editing treatments, such as <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic">one recently used to treat baby KJ Muldoon</a>, are designed to correct one mutation at a time. The scientists worked on correcting all five mutations, streamlining experiments, saving resources, and testing the robustness of the underlying science.</p> <p>“We developed a robust framework to correct multiple mutations in parallel,” said Alexander Sousa, a postdoctoral fellow in the Liu lab and one of three co-first authors along with Holt Sakai of the Liu lab and Markus Terrey of The Jackson Laboratory. “This effort was really about creating a blueprint that could be rapidly applied to other rare diseases too.”</p> <p>The researchers first tested their strategies in cultured cells from patients with AHC. They demonstrated that they could correctly repair AHC mutations in up to 90 percent of treated cells, with minimal changes to other stretches of DNA. </p> <p>Next, the group collaborated with Jackson Lab researchers to test their treatments in two mouse models of AHC, which carry <em>Atp1a3 </em>mutations similar to those in patients with AHC. Without treatment, the mice developed seizures, movement problems, and died prematurely. When the scientists injected their editing system into the brains of the animals, their symptoms disappeared or were substantially reduced. Treated mice survived more than twice as long as untreated animals. Moreover, the function of their Atp1a3 protein was restored in the brain, and their motor and cognitive deficits were ameliorated. The scientists delivered the prime editors to cells in mice using clinically validated viruses called AAVs, which are already used in FDA-approved gene therapies targeting brain cells.</p> <p>“The results really exceeded our expectations,” said Sakai. “It was incredibly exciting to see that data.”</p> <p>The team also tested traditional gene therapy, which delivered an extra, healthy copy of the <em>ATP1A3 </em>gene to cells, and found that symptoms did not improve in animals. This finding highlights the unique advantage of using gene editing to directly correct a mutation that results in a malfunctioning, disease-causing protein, the researchers said. </p> <p>“Before this study, we didn’t even know if we could intervene in AHC after birth in an animal,” said Sousa. “Now we know you can.”</p> <h2>A template for rare diseases</h2> <p>Because the treatment required direct injection into the brain shortly after birth, the team is now exploring less invasive delivery methods, and whether treatment later in life could still be effective. </p> <p>Beyond AHC, the team sees their approach as a template for tackling other rare genetic diseases — especially those that affect the brain. With the ability to rapidly design and test multiple gene editing treatments at once, they hope to bring the same precision and speed to many other conditions.</p> <p>“This is a powerful proof of concept,” said Sakai. “It shows that we can use prime editing to treat genetic brain diseases, and it lays the groundwork for translating this approach to the clinic.”<br>  </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>Support for the study was provided by the National Institutes of Health, the Chan-Zuckerberg Initiative, RARE Hope, the Alternating Hemiplegia of Childhood Foundation, the For Henry AHC Foundation, the Davis Family Foundation, the Toolbox Foundation L2C Initiative, the Cure AHC Foundation, the Howard Hughes Medical Institute, and the National Science 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>Sousa AA, Terrey M, Sakai HA et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank">In vivo prime editing rescues alternating hemiplegia of childhood in mice</a>. <em>Cell</em>. Online July 21, 2025. DOI: 10.1016/j.cell.2025.06.038</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/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, 11 Mar 2025 13:18:28 +0000 Corie Lok 5558201 at Gene editing extends lifespan in mouse model of prion disease /news/gene-editing-extends-lifespan-mouse-model-prion-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Prime editing treats childhood brain disease in mice</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Corie Lok</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-07-21T11:37:05-04:00" class="datetime">July 21, 2025</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>Prime editing treats childhood brain disease in mice</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>Scientists use a precise form of gene editing called prime editing to correct the most common genetic mutations that cause alternating hemiplegia of childhood, a rare and severe neurological disorder that begins in infancy.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Sarah C.P. Williams </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="2025-07-21T11:37:05-04:00" title="Monday, July 21, 2025 - 11:37" class="datetime">July 21, 2025</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> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=4v-1bgTe 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=vcca1mnQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=EgQptYlI 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9" 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" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Kathleen Sweadner, Christine Simmons, and Alfred George </div> <div class="media-caption__description"> Scientists studied cultured human neurons, shown here under a microscope, that have a protein (green) with a mutation that causes alternating hemiplegia of childhood. </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/619/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 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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-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>Related news</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/prime-editing-efficiently-corrects-cystic-fibrosis-mutation-human-lung-cells" class="node"> <div class="field field--name-field-image 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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"> <a href="/news/prime-editing-shows-proof-concept-treating-sickle-cell-disease"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2023/24170591501_3be68fd5a6_o.jpg?itok=_OtIoGoJ 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/2023/24170591501_3be68fd5a6_o.jpg?itok=_OtIoGoJ 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/2023/24170591501_3be68fd5a6_o.jpg?itok=oNPuC_bT 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/2023/24170591501_3be68fd5a6_o.jpg?itok=oNPuC_bT 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/2023/24170591501_3be68fd5a6_o.jpg?itok=hKqIKriQ 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/2023/24170591501_3be68fd5a6_o.jpg?itok=iAbN4a54 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2023/24170591501_3be68fd5a6_o.jpg?itok=iAbN4a54" alt="Sickle cell disease" title="Sickle cell disease" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/prime-editing-shows-proof-concept-treating-sickle-cell-disease" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Prime editing shows proof of concept for treating sickle cell disease</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/improved-prime-editing-system-makes-gene-sized-edits-human-cells-therapeutic-levels" 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"> <a href="/news/improved-prime-editing-system-makes-gene-sized-edits-human-cells-therapeutic-levels"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=---0ZBF7 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/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=---0ZBF7 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/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=o0ilCOx1 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/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=o0ilCOx1 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/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=_VAtunv8 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/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=HMplbY8o 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=HMplbY8o" alt="Graphic displaying a green protein filling a gap in railroad tracks that are colored like DNA." title="Graphic displaying a green protein filling a gap in railroad tracks that are colored like DNA." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/improved-prime-editing-system-makes-gene-sized-edits-human-cells-therapeutic-levels" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Improved prime editing system makes gene-sized edits in human cells at therapeutic levels</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/new-prime-editing-system-inserts-entire-genes-human-cells" 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"> <a href="/news/new-prime-editing-system-inserts-entire-genes-human-cells"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/TwinPE-07.jpg?h=9423a5c0&itok=hCpTpO4i 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=hCpTpO4i 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=JBB_oOB9 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=JBB_oOB9 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=XOGiyqIC 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=l-wsLX11 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/TwinPE-07.jpg?h=9423a5c0&itok=l-wsLX11" alt="Ricardo Job-Reese, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/new-prime-editing-system-inserts-entire-genes-human-cells" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">New prime editing system inserts entire genes in human cells</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" 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"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=ffrhaQKJ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj" alt="Susanna Hamilton, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Next generation prime editing systems move closer to possible therapeutic applications</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>By the time they are a few months old, infants born with alternating hemiplegia of childhood (AHC) begin experiencing terrifying episodes of paralysis and seizures, and will soon show developmental delays and intellectual disability. There is no cure or effective treatment for this rare genetic disease, but new research suggests a potential path to one. </p> <p>Researchers at the ӳý and The Jackson Laboratory have used prime editing, a precise and versatile form of gene editing, to correct the root cause of AHC in mice. The team used a scalable approach to develop prime editing treatments that directly repaired five different AHC-causing genetic mutations. Mice that received the treatment had far fewer and less severe symptoms of AHC, and survived more than twice as long as untreated mice. </p> <p>The new study, published in <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank"><em>Cell</em></a>, is the first time prime editing has been used to treat a neurological disease in animals, offering hope for treating people with AHC and other genetic brain disorders. <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">Prime editing was developed in 2019</a> by the lab of <a href="/bios/david-liu">David Liu</a>, a ӳý core institute member and co-senior author of the new paper. The technology has already been successfully tested in a clinical trial for another rare genetic disease.</p> <p>“This study is an important milestone for prime editing and one of the most exciting examples of therapeutic gene editing to come from our team,” said Liu, Richard Merkin Professor and director of the <a href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute of Transformative Technologies in Healthcare at the ӳý</a>. “It opens the door to one day repairing the underlying genetic causes of many neurological disorders that have long been considered untreatable.” Liu is also a Howard Hughes Medical Institute investigator and a professor at Harvard University.</p> <p>The ability to precisely edit DNA directly in the brain has important implications for neurological diseases, said Cathleen Lutz, vice president of the Rare Disease Translational Center at The Jackson Laboratory and co-senior author of the study. “This level of editing efficiency in the brain is really quite remarkable.”</p> <p>The team’s patient partner is RARE Hope (formerly Hope for Annabel), a non-profit focused on accelerating research on AHC and developing scalable, patient-centric research platforms to benefit the larger rare disease community. RARE Hope initiated the collaboration and was closely engaged throughout the project. </p> <p>“This study is a win not just for our community but for all rare neurological conditions, and a breakthrough moment in expanding access to a broader cohort of potential patients,” said Nina Frost, founder and president of RARE Hope, a co-author of the study, and mother of a daughter with AHC. “It’s been a privilege to collaborate on such a scientifically significant effort with a team that has kept patients at the center of proof-of-concept research — engaging the patient community, modeling the patient experience, and integrating patient priorities into experimental design. This is a model for patient-relevant, patient-centered research because the team included us as true partners.”</p> <h2>Brain gene editing</h2> <p>The vast majority of AHC cases are caused by one of four mutations in <em>ATP1A3</em>, a gene essential for brain cell function. In the new work, Liu’s team set out to simultaneously develop prime editing treatments that could fix five <em>ATP1A3 </em>mutations, including the four most common — a scale rarely attempted in therapeutic gene editing research. Most other gene editing treatments, such as <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic">one recently used to treat baby KJ Muldoon</a>, are designed to correct one mutation at a time. The scientists worked on correcting all five mutations, streamlining experiments, saving resources, and testing the robustness of the underlying science.</p> <p>“We developed a robust framework to correct multiple mutations in parallel,” said Alexander Sousa, a postdoctoral fellow in the Liu lab and one of three co-first authors along with Holt Sakai of the Liu lab and Markus Terrey of The Jackson Laboratory. “This effort was really about creating a blueprint that could be rapidly applied to other rare diseases too.”</p> <p>The researchers first tested their strategies in cultured cells from patients with AHC. They demonstrated that they could correctly repair AHC mutations in up to 90 percent of treated cells, with minimal changes to other stretches of DNA. </p> <p>Next, the group collaborated with Jackson Lab researchers to test their treatments in two mouse models of AHC, which carry <em>Atp1a3 </em>mutations similar to those in patients with AHC. Without treatment, the mice developed seizures, movement problems, and died prematurely. When the scientists injected their editing system into the brains of the animals, their symptoms disappeared or were substantially reduced. Treated mice survived more than twice as long as untreated animals. Moreover, the function of their Atp1a3 protein was restored in the brain, and their motor and cognitive deficits were ameliorated. The scientists delivered the prime editors to cells in mice using clinically validated viruses called AAVs, which are already used in FDA-approved gene therapies targeting brain cells.</p> <p>“The results really exceeded our expectations,” said Sakai. “It was incredibly exciting to see that data.”</p> <p>The team also tested traditional gene therapy, which delivered an extra, healthy copy of the <em>ATP1A3 </em>gene to cells, and found that symptoms did not improve in animals. This finding highlights the unique advantage of using gene editing to directly correct a mutation that results in a malfunctioning, disease-causing protein, the researchers said. </p> <p>“Before this study, we didn’t even know if we could intervene in AHC after birth in an animal,” said Sousa. “Now we know you can.”</p> <h2>A template for rare diseases</h2> <p>Because the treatment required direct injection into the brain shortly after birth, the team is now exploring less invasive delivery methods, and whether treatment later in life could still be effective. </p> <p>Beyond AHC, the team sees their approach as a template for tackling other rare genetic diseases — especially those that affect the brain. With the ability to rapidly design and test multiple gene editing treatments at once, they hope to bring the same precision and speed to many other conditions.</p> <p>“This is a powerful proof of concept,” said Sakai. “It shows that we can use prime editing to treat genetic brain diseases, and it lays the groundwork for translating this approach to the clinic.”<br>  </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>Support for the study was provided by the National Institutes of Health, the Chan-Zuckerberg Initiative, RARE Hope, the Alternating Hemiplegia of Childhood Foundation, the For Henry AHC Foundation, the Davis Family Foundation, the Toolbox Foundation L2C Initiative, the Cure AHC Foundation, the Howard Hughes Medical Institute, and the National Science 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>Sousa AA, Terrey M, Sakai HA et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank">In vivo prime editing rescues alternating hemiplegia of childhood in mice</a>. <em>Cell</em>. Online July 21, 2025. DOI: 10.1016/j.cell.2025.06.038</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/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 Jan 2025 10:00:00 +0000 adicorat 5558086 at A clinical genomicist harnesses team-based science to help rare-disease patients /news/clinical-genomicist-harnesses-team-based-science-help-rare-disease-patients <span class="field field--name-title field--type-string field--label-hidden"><h1>Prime editing treats childhood brain disease in mice</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Corie Lok</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-07-21T11:37:05-04:00" class="datetime">July 21, 2025</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>Prime editing treats childhood brain disease in mice</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>Scientists use a precise form of gene editing called prime editing to correct the most common genetic mutations that cause alternating hemiplegia of childhood, a rare and severe neurological disorder that begins in infancy.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Sarah C.P. Williams </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="2025-07-21T11:37:05-04:00" title="Monday, July 21, 2025 - 11:37" class="datetime">July 21, 2025</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> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=4v-1bgTe 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=vcca1mnQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=EgQptYlI 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9" 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" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Kathleen Sweadner, Christine Simmons, and Alfred George </div> <div class="media-caption__description"> Scientists studied cultured human neurons, shown here under a microscope, that have a protein (green) with a mutation that causes alternating hemiplegia of childhood. </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/619/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 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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-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>Related news</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/prime-editing-efficiently-corrects-cystic-fibrosis-mutation-human-lung-cells" class="node"> <div class="field field--name-field-image 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field__item"> <a href="/news/improved-prime-editing-system-makes-gene-sized-edits-human-cells-therapeutic-levels"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=---0ZBF7 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/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=---0ZBF7 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/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=o0ilCOx1 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="87" height="104"/> <source 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in railroad tracks that are colored like DNA." title="Graphic displaying a green protein filling a gap in railroad tracks that are colored like DNA." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/improved-prime-editing-system-makes-gene-sized-edits-human-cells-therapeutic-levels" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Improved prime editing system makes gene-sized edits in human cells at therapeutic levels</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/new-prime-editing-system-inserts-entire-genes-human-cells" 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"> <a href="/news/new-prime-editing-system-inserts-entire-genes-human-cells"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/TwinPE-07.jpg?h=9423a5c0&itok=hCpTpO4i 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=hCpTpO4i 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=JBB_oOB9 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=JBB_oOB9 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=XOGiyqIC 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=l-wsLX11 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/TwinPE-07.jpg?h=9423a5c0&itok=l-wsLX11" alt="Ricardo Job-Reese, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/new-prime-editing-system-inserts-entire-genes-human-cells" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">New prime editing system inserts entire genes in human cells</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" 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"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=ffrhaQKJ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj" alt="Susanna Hamilton, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Next generation prime editing systems move closer to possible therapeutic applications</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>By the time they are a few months old, infants born with alternating hemiplegia of childhood (AHC) begin experiencing terrifying episodes of paralysis and seizures, and will soon show developmental delays and intellectual disability. There is no cure or effective treatment for this rare genetic disease, but new research suggests a potential path to one. </p> <p>Researchers at the ӳý and The Jackson Laboratory have used prime editing, a precise and versatile form of gene editing, to correct the root cause of AHC in mice. The team used a scalable approach to develop prime editing treatments that directly repaired five different AHC-causing genetic mutations. Mice that received the treatment had far fewer and less severe symptoms of AHC, and survived more than twice as long as untreated mice. </p> <p>The new study, published in <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank"><em>Cell</em></a>, is the first time prime editing has been used to treat a neurological disease in animals, offering hope for treating people with AHC and other genetic brain disorders. <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">Prime editing was developed in 2019</a> by the lab of <a href="/bios/david-liu">David Liu</a>, a ӳý core institute member and co-senior author of the new paper. The technology has already been successfully tested in a clinical trial for another rare genetic disease.</p> <p>“This study is an important milestone for prime editing and one of the most exciting examples of therapeutic gene editing to come from our team,” said Liu, Richard Merkin Professor and director of the <a href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute of Transformative Technologies in Healthcare at the ӳý</a>. “It opens the door to one day repairing the underlying genetic causes of many neurological disorders that have long been considered untreatable.” Liu is also a Howard Hughes Medical Institute investigator and a professor at Harvard University.</p> <p>The ability to precisely edit DNA directly in the brain has important implications for neurological diseases, said Cathleen Lutz, vice president of the Rare Disease Translational Center at The Jackson Laboratory and co-senior author of the study. “This level of editing efficiency in the brain is really quite remarkable.”</p> <p>The team’s patient partner is RARE Hope (formerly Hope for Annabel), a non-profit focused on accelerating research on AHC and developing scalable, patient-centric research platforms to benefit the larger rare disease community. RARE Hope initiated the collaboration and was closely engaged throughout the project. </p> <p>“This study is a win not just for our community but for all rare neurological conditions, and a breakthrough moment in expanding access to a broader cohort of potential patients,” said Nina Frost, founder and president of RARE Hope, a co-author of the study, and mother of a daughter with AHC. “It’s been a privilege to collaborate on such a scientifically significant effort with a team that has kept patients at the center of proof-of-concept research — engaging the patient community, modeling the patient experience, and integrating patient priorities into experimental design. This is a model for patient-relevant, patient-centered research because the team included us as true partners.”</p> <h2>Brain gene editing</h2> <p>The vast majority of AHC cases are caused by one of four mutations in <em>ATP1A3</em>, a gene essential for brain cell function. In the new work, Liu’s team set out to simultaneously develop prime editing treatments that could fix five <em>ATP1A3 </em>mutations, including the four most common — a scale rarely attempted in therapeutic gene editing research. Most other gene editing treatments, such as <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic">one recently used to treat baby KJ Muldoon</a>, are designed to correct one mutation at a time. The scientists worked on correcting all five mutations, streamlining experiments, saving resources, and testing the robustness of the underlying science.</p> <p>“We developed a robust framework to correct multiple mutations in parallel,” said Alexander Sousa, a postdoctoral fellow in the Liu lab and one of three co-first authors along with Holt Sakai of the Liu lab and Markus Terrey of The Jackson Laboratory. “This effort was really about creating a blueprint that could be rapidly applied to other rare diseases too.”</p> <p>The researchers first tested their strategies in cultured cells from patients with AHC. They demonstrated that they could correctly repair AHC mutations in up to 90 percent of treated cells, with minimal changes to other stretches of DNA. </p> <p>Next, the group collaborated with Jackson Lab researchers to test their treatments in two mouse models of AHC, which carry <em>Atp1a3 </em>mutations similar to those in patients with AHC. Without treatment, the mice developed seizures, movement problems, and died prematurely. When the scientists injected their editing system into the brains of the animals, their symptoms disappeared or were substantially reduced. Treated mice survived more than twice as long as untreated animals. Moreover, the function of their Atp1a3 protein was restored in the brain, and their motor and cognitive deficits were ameliorated. The scientists delivered the prime editors to cells in mice using clinically validated viruses called AAVs, which are already used in FDA-approved gene therapies targeting brain cells.</p> <p>“The results really exceeded our expectations,” said Sakai. “It was incredibly exciting to see that data.”</p> <p>The team also tested traditional gene therapy, which delivered an extra, healthy copy of the <em>ATP1A3 </em>gene to cells, and found that symptoms did not improve in animals. This finding highlights the unique advantage of using gene editing to directly correct a mutation that results in a malfunctioning, disease-causing protein, the researchers said. </p> <p>“Before this study, we didn’t even know if we could intervene in AHC after birth in an animal,” said Sousa. “Now we know you can.”</p> <h2>A template for rare diseases</h2> <p>Because the treatment required direct injection into the brain shortly after birth, the team is now exploring less invasive delivery methods, and whether treatment later in life could still be effective. </p> <p>Beyond AHC, the team sees their approach as a template for tackling other rare genetic diseases — especially those that affect the brain. With the ability to rapidly design and test multiple gene editing treatments at once, they hope to bring the same precision and speed to many other conditions.</p> <p>“This is a powerful proof of concept,” said Sakai. “It shows that we can use prime editing to treat genetic brain diseases, and it lays the groundwork for translating this approach to the clinic.”<br>  </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>Support for the study was provided by the National Institutes of Health, the Chan-Zuckerberg Initiative, RARE Hope, the Alternating Hemiplegia of Childhood Foundation, the For Henry AHC Foundation, the Davis Family Foundation, the Toolbox Foundation L2C Initiative, the Cure AHC Foundation, the Howard Hughes Medical Institute, and the National Science 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>Sousa AA, Terrey M, Sakai HA et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank">In vivo prime editing rescues alternating hemiplegia of childhood in mice</a>. <em>Cell</em>. Online July 21, 2025. DOI: 10.1016/j.cell.2025.06.038</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/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, 07 Jan 2025 14:00:00 +0000 adicorat 5557606 at Researchers engineer in vivo delivery system for prime editing, partially restoring vision in mice /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>Prime editing treats childhood brain disease in mice</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Corie Lok</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-07-21T11:37:05-04:00" class="datetime">July 21, 2025</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>Prime editing treats childhood brain disease in mice</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>Scientists use a precise form of gene editing called prime editing to correct the most common genetic mutations that cause alternating hemiplegia of childhood, a rare and severe neurological disorder that begins in infancy.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Sarah C.P. Williams </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="2025-07-21T11:37:05-04:00" title="Monday, July 21, 2025 - 11:37" class="datetime">July 21, 2025</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> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=4v-1bgTe 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=vcca1mnQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=EgQptYlI 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9" 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" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Kathleen Sweadner, Christine Simmons, and Alfred George </div> <div class="media-caption__description"> Scientists studied cultured human neurons, shown here under a microscope, that have a protein (green) with a mutation that causes alternating hemiplegia of childhood. </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/619/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 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type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2021/TwinPE-07.jpg?h=9423a5c0&itok=XOGiyqIC 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=l-wsLX11 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/TwinPE-07.jpg?h=9423a5c0&itok=l-wsLX11" alt="Ricardo Job-Reese, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/new-prime-editing-system-inserts-entire-genes-human-cells" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">New prime editing system inserts entire genes in human cells</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" 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"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=ffrhaQKJ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj" alt="Susanna Hamilton, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Next generation prime editing systems move closer to possible therapeutic applications</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>By the time they are a few months old, infants born with alternating hemiplegia of childhood (AHC) begin experiencing terrifying episodes of paralysis and seizures, and will soon show developmental delays and intellectual disability. There is no cure or effective treatment for this rare genetic disease, but new research suggests a potential path to one. </p> <p>Researchers at the ӳý and The Jackson Laboratory have used prime editing, a precise and versatile form of gene editing, to correct the root cause of AHC in mice. The team used a scalable approach to develop prime editing treatments that directly repaired five different AHC-causing genetic mutations. Mice that received the treatment had far fewer and less severe symptoms of AHC, and survived more than twice as long as untreated mice. </p> <p>The new study, published in <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank"><em>Cell</em></a>, is the first time prime editing has been used to treat a neurological disease in animals, offering hope for treating people with AHC and other genetic brain disorders. <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">Prime editing was developed in 2019</a> by the lab of <a href="/bios/david-liu">David Liu</a>, a ӳý core institute member and co-senior author of the new paper. The technology has already been successfully tested in a clinical trial for another rare genetic disease.</p> <p>“This study is an important milestone for prime editing and one of the most exciting examples of therapeutic gene editing to come from our team,” said Liu, Richard Merkin Professor and director of the <a href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute of Transformative Technologies in Healthcare at the ӳý</a>. “It opens the door to one day repairing the underlying genetic causes of many neurological disorders that have long been considered untreatable.” Liu is also a Howard Hughes Medical Institute investigator and a professor at Harvard University.</p> <p>The ability to precisely edit DNA directly in the brain has important implications for neurological diseases, said Cathleen Lutz, vice president of the Rare Disease Translational Center at The Jackson Laboratory and co-senior author of the study. “This level of editing efficiency in the brain is really quite remarkable.”</p> <p>The team’s patient partner is RARE Hope (formerly Hope for Annabel), a non-profit focused on accelerating research on AHC and developing scalable, patient-centric research platforms to benefit the larger rare disease community. RARE Hope initiated the collaboration and was closely engaged throughout the project. </p> <p>“This study is a win not just for our community but for all rare neurological conditions, and a breakthrough moment in expanding access to a broader cohort of potential patients,” said Nina Frost, founder and president of RARE Hope, a co-author of the study, and mother of a daughter with AHC. “It’s been a privilege to collaborate on such a scientifically significant effort with a team that has kept patients at the center of proof-of-concept research — engaging the patient community, modeling the patient experience, and integrating patient priorities into experimental design. This is a model for patient-relevant, patient-centered research because the team included us as true partners.”</p> <h2>Brain gene editing</h2> <p>The vast majority of AHC cases are caused by one of four mutations in <em>ATP1A3</em>, a gene essential for brain cell function. In the new work, Liu’s team set out to simultaneously develop prime editing treatments that could fix five <em>ATP1A3 </em>mutations, including the four most common — a scale rarely attempted in therapeutic gene editing research. Most other gene editing treatments, such as <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic">one recently used to treat baby KJ Muldoon</a>, are designed to correct one mutation at a time. The scientists worked on correcting all five mutations, streamlining experiments, saving resources, and testing the robustness of the underlying science.</p> <p>“We developed a robust framework to correct multiple mutations in parallel,” said Alexander Sousa, a postdoctoral fellow in the Liu lab and one of three co-first authors along with Holt Sakai of the Liu lab and Markus Terrey of The Jackson Laboratory. “This effort was really about creating a blueprint that could be rapidly applied to other rare diseases too.”</p> <p>The researchers first tested their strategies in cultured cells from patients with AHC. They demonstrated that they could correctly repair AHC mutations in up to 90 percent of treated cells, with minimal changes to other stretches of DNA. </p> <p>Next, the group collaborated with Jackson Lab researchers to test their treatments in two mouse models of AHC, which carry <em>Atp1a3 </em>mutations similar to those in patients with AHC. Without treatment, the mice developed seizures, movement problems, and died prematurely. When the scientists injected their editing system into the brains of the animals, their symptoms disappeared or were substantially reduced. Treated mice survived more than twice as long as untreated animals. Moreover, the function of their Atp1a3 protein was restored in the brain, and their motor and cognitive deficits were ameliorated. The scientists delivered the prime editors to cells in mice using clinically validated viruses called AAVs, which are already used in FDA-approved gene therapies targeting brain cells.</p> <p>“The results really exceeded our expectations,” said Sakai. “It was incredibly exciting to see that data.”</p> <p>The team also tested traditional gene therapy, which delivered an extra, healthy copy of the <em>ATP1A3 </em>gene to cells, and found that symptoms did not improve in animals. This finding highlights the unique advantage of using gene editing to directly correct a mutation that results in a malfunctioning, disease-causing protein, the researchers said. </p> <p>“Before this study, we didn’t even know if we could intervene in AHC after birth in an animal,” said Sousa. “Now we know you can.”</p> <h2>A template for rare diseases</h2> <p>Because the treatment required direct injection into the brain shortly after birth, the team is now exploring less invasive delivery methods, and whether treatment later in life could still be effective. </p> <p>Beyond AHC, the team sees their approach as a template for tackling other rare genetic diseases — especially those that affect the brain. With the ability to rapidly design and test multiple gene editing treatments at once, they hope to bring the same precision and speed to many other conditions.</p> <p>“This is a powerful proof of concept,” said Sakai. “It shows that we can use prime editing to treat genetic brain diseases, and it lays the groundwork for translating this approach to the clinic.”<br>  </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>Support for the study was provided by the National Institutes of Health, the Chan-Zuckerberg Initiative, RARE Hope, the Alternating Hemiplegia of Childhood Foundation, the For Henry AHC Foundation, the Davis Family Foundation, the Toolbox Foundation L2C Initiative, the Cure AHC Foundation, the Howard Hughes Medical Institute, and the National Science 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>Sousa AA, Terrey M, Sakai HA et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank">In vivo prime editing rescues alternating hemiplegia of childhood in mice</a>. <em>Cell</em>. Online July 21, 2025. DOI: 10.1016/j.cell.2025.06.038</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/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 Approach studies how rare gene variant pairs contribute to disease /news/approach-studies-how-rare-gene-variant-pairs-contribute-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Prime editing treats childhood brain disease in mice</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Corie Lok</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-07-21T11:37:05-04:00" class="datetime">July 21, 2025</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>Prime editing treats childhood brain disease in mice</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>Scientists use a precise form of gene editing called prime editing to correct the most common genetic mutations that cause alternating hemiplegia of childhood, a rare and severe neurological disorder that begins in infancy.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Sarah C.P. Williams </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="2025-07-21T11:37:05-04:00" title="Monday, July 21, 2025 - 11:37" class="datetime">July 21, 2025</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> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=4v-1bgTe 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=vcca1mnQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=EgQptYlI 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9" 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" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Kathleen Sweadner, Christine Simmons, and Alfred George </div> <div class="media-caption__description"> Scientists studied cultured human neurons, shown here under a microscope, that have a protein (green) with a mutation that causes alternating hemiplegia of childhood. </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/619/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 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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-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>Related news</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/prime-editing-efficiently-corrects-cystic-fibrosis-mutation-human-lung-cells" class="node"> <div class="field field--name-field-image 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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"> <a href="/news/prime-editing-shows-proof-concept-treating-sickle-cell-disease"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2023/24170591501_3be68fd5a6_o.jpg?itok=_OtIoGoJ 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/2023/24170591501_3be68fd5a6_o.jpg?itok=_OtIoGoJ 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/2023/24170591501_3be68fd5a6_o.jpg?itok=oNPuC_bT 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/2023/24170591501_3be68fd5a6_o.jpg?itok=oNPuC_bT 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/2023/24170591501_3be68fd5a6_o.jpg?itok=hKqIKriQ 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/2023/24170591501_3be68fd5a6_o.jpg?itok=iAbN4a54 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2023/24170591501_3be68fd5a6_o.jpg?itok=iAbN4a54" alt="Sickle cell disease" title="Sickle cell disease" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/prime-editing-shows-proof-concept-treating-sickle-cell-disease" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Prime editing shows proof of concept for treating sickle cell disease</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/improved-prime-editing-system-makes-gene-sized-edits-human-cells-therapeutic-levels" 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"> <a href="/news/improved-prime-editing-system-makes-gene-sized-edits-human-cells-therapeutic-levels"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/longstory/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=---0ZBF7 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/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=---0ZBF7 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/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=o0ilCOx1 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/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=o0ilCOx1 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/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=_VAtunv8 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/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=HMplbY8o 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=HMplbY8o" alt="Graphic displaying a green protein filling a gap in railroad tracks that are colored like DNA." title="Graphic displaying a green protein filling a gap in railroad tracks that are colored like DNA." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/improved-prime-editing-system-makes-gene-sized-edits-human-cells-therapeutic-levels" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Improved prime editing system makes gene-sized edits in human cells at therapeutic levels</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/new-prime-editing-system-inserts-entire-genes-human-cells" 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"> <a href="/news/new-prime-editing-system-inserts-entire-genes-human-cells"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/TwinPE-07.jpg?h=9423a5c0&itok=hCpTpO4i 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=hCpTpO4i 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=JBB_oOB9 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=JBB_oOB9 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=XOGiyqIC 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=l-wsLX11 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/TwinPE-07.jpg?h=9423a5c0&itok=l-wsLX11" alt="Ricardo Job-Reese, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/new-prime-editing-system-inserts-entire-genes-human-cells" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">New prime editing system inserts entire genes in human cells</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" 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"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=ffrhaQKJ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj" alt="Susanna Hamilton, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Next generation prime editing systems move closer to possible therapeutic applications</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>By the time they are a few months old, infants born with alternating hemiplegia of childhood (AHC) begin experiencing terrifying episodes of paralysis and seizures, and will soon show developmental delays and intellectual disability. There is no cure or effective treatment for this rare genetic disease, but new research suggests a potential path to one. </p> <p>Researchers at the ӳý and The Jackson Laboratory have used prime editing, a precise and versatile form of gene editing, to correct the root cause of AHC in mice. The team used a scalable approach to develop prime editing treatments that directly repaired five different AHC-causing genetic mutations. Mice that received the treatment had far fewer and less severe symptoms of AHC, and survived more than twice as long as untreated mice. </p> <p>The new study, published in <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank"><em>Cell</em></a>, is the first time prime editing has been used to treat a neurological disease in animals, offering hope for treating people with AHC and other genetic brain disorders. <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">Prime editing was developed in 2019</a> by the lab of <a href="/bios/david-liu">David Liu</a>, a ӳý core institute member and co-senior author of the new paper. The technology has already been successfully tested in a clinical trial for another rare genetic disease.</p> <p>“This study is an important milestone for prime editing and one of the most exciting examples of therapeutic gene editing to come from our team,” said Liu, Richard Merkin Professor and director of the <a href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute of Transformative Technologies in Healthcare at the ӳý</a>. “It opens the door to one day repairing the underlying genetic causes of many neurological disorders that have long been considered untreatable.” Liu is also a Howard Hughes Medical Institute investigator and a professor at Harvard University.</p> <p>The ability to precisely edit DNA directly in the brain has important implications for neurological diseases, said Cathleen Lutz, vice president of the Rare Disease Translational Center at The Jackson Laboratory and co-senior author of the study. “This level of editing efficiency in the brain is really quite remarkable.”</p> <p>The team’s patient partner is RARE Hope (formerly Hope for Annabel), a non-profit focused on accelerating research on AHC and developing scalable, patient-centric research platforms to benefit the larger rare disease community. RARE Hope initiated the collaboration and was closely engaged throughout the project. </p> <p>“This study is a win not just for our community but for all rare neurological conditions, and a breakthrough moment in expanding access to a broader cohort of potential patients,” said Nina Frost, founder and president of RARE Hope, a co-author of the study, and mother of a daughter with AHC. “It’s been a privilege to collaborate on such a scientifically significant effort with a team that has kept patients at the center of proof-of-concept research — engaging the patient community, modeling the patient experience, and integrating patient priorities into experimental design. This is a model for patient-relevant, patient-centered research because the team included us as true partners.”</p> <h2>Brain gene editing</h2> <p>The vast majority of AHC cases are caused by one of four mutations in <em>ATP1A3</em>, a gene essential for brain cell function. In the new work, Liu’s team set out to simultaneously develop prime editing treatments that could fix five <em>ATP1A3 </em>mutations, including the four most common — a scale rarely attempted in therapeutic gene editing research. Most other gene editing treatments, such as <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic">one recently used to treat baby KJ Muldoon</a>, are designed to correct one mutation at a time. The scientists worked on correcting all five mutations, streamlining experiments, saving resources, and testing the robustness of the underlying science.</p> <p>“We developed a robust framework to correct multiple mutations in parallel,” said Alexander Sousa, a postdoctoral fellow in the Liu lab and one of three co-first authors along with Holt Sakai of the Liu lab and Markus Terrey of The Jackson Laboratory. “This effort was really about creating a blueprint that could be rapidly applied to other rare diseases too.”</p> <p>The researchers first tested their strategies in cultured cells from patients with AHC. They demonstrated that they could correctly repair AHC mutations in up to 90 percent of treated cells, with minimal changes to other stretches of DNA. </p> <p>Next, the group collaborated with Jackson Lab researchers to test their treatments in two mouse models of AHC, which carry <em>Atp1a3 </em>mutations similar to those in patients with AHC. Without treatment, the mice developed seizures, movement problems, and died prematurely. When the scientists injected their editing system into the brains of the animals, their symptoms disappeared or were substantially reduced. Treated mice survived more than twice as long as untreated animals. Moreover, the function of their Atp1a3 protein was restored in the brain, and their motor and cognitive deficits were ameliorated. The scientists delivered the prime editors to cells in mice using clinically validated viruses called AAVs, which are already used in FDA-approved gene therapies targeting brain cells.</p> <p>“The results really exceeded our expectations,” said Sakai. “It was incredibly exciting to see that data.”</p> <p>The team also tested traditional gene therapy, which delivered an extra, healthy copy of the <em>ATP1A3 </em>gene to cells, and found that symptoms did not improve in animals. This finding highlights the unique advantage of using gene editing to directly correct a mutation that results in a malfunctioning, disease-causing protein, the researchers said. </p> <p>“Before this study, we didn’t even know if we could intervene in AHC after birth in an animal,” said Sousa. “Now we know you can.”</p> <h2>A template for rare diseases</h2> <p>Because the treatment required direct injection into the brain shortly after birth, the team is now exploring less invasive delivery methods, and whether treatment later in life could still be effective. </p> <p>Beyond AHC, the team sees their approach as a template for tackling other rare genetic diseases — especially those that affect the brain. With the ability to rapidly design and test multiple gene editing treatments at once, they hope to bring the same precision and speed to many other conditions.</p> <p>“This is a powerful proof of concept,” said Sakai. “It shows that we can use prime editing to treat genetic brain diseases, and it lays the groundwork for translating this approach to the clinic.”<br>  </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>Support for the study was provided by the National Institutes of Health, the Chan-Zuckerberg Initiative, RARE Hope, the Alternating Hemiplegia of Childhood Foundation, the For Henry AHC Foundation, the Davis Family Foundation, the Toolbox Foundation L2C Initiative, the Cure AHC Foundation, the Howard Hughes Medical Institute, and the National Science 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>Sousa AA, Terrey M, Sakai HA et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank">In vivo prime editing rescues alternating hemiplegia of childhood in mice</a>. <em>Cell</em>. Online July 21, 2025. DOI: 10.1016/j.cell.2025.06.038</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/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, 07 Dec 2023 17:04:15 +0000 tulrich@broadinstitute.org 5556176 at #WhyIScience Q&A: A computational biologist helps build datasets for genetic disease diagnosis /news/whyiscience-qa-computational-biologist-helps-build-datasets-genetic-disease-diagnosis <span class="field field--name-title field--type-string field--label-hidden"><h1>Prime editing treats childhood brain disease in mice</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Corie Lok</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-07-21T11:37:05-04:00" class="datetime">July 21, 2025</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>Prime editing treats childhood brain disease in mice</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>Scientists use a precise form of gene editing called prime editing to correct the most common genetic mutations that cause alternating hemiplegia of childhood, a rare and severe neurological disorder that begins in infancy.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Sarah C.P. Williams </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="2025-07-21T11:37:05-04:00" title="Monday, July 21, 2025 - 11:37" class="datetime">July 21, 2025</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> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=4v-1bgTe 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=vcca1mnQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=EgQptYlI 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9" 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" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Kathleen Sweadner, Christine Simmons, and Alfred George </div> <div class="media-caption__description"> Scientists studied cultured human neurons, shown here under a microscope, that have a protein (green) with a mutation that causes alternating hemiplegia of childhood. </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/619/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 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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-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>Related news</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/prime-editing-efficiently-corrects-cystic-fibrosis-mutation-human-lung-cells" class="node"> <div class="field field--name-field-image 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href="/news/new-prime-editing-system-inserts-entire-genes-human-cells"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/TwinPE-07.jpg?h=9423a5c0&itok=hCpTpO4i 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=hCpTpO4i 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=JBB_oOB9 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=JBB_oOB9 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=XOGiyqIC 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=l-wsLX11 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/TwinPE-07.jpg?h=9423a5c0&itok=l-wsLX11" alt="Ricardo Job-Reese, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/new-prime-editing-system-inserts-entire-genes-human-cells" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">New prime editing system inserts entire genes in human cells</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" 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"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=ffrhaQKJ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj" alt="Susanna Hamilton, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Next generation prime editing systems move closer to possible therapeutic applications</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>By the time they are a few months old, infants born with alternating hemiplegia of childhood (AHC) begin experiencing terrifying episodes of paralysis and seizures, and will soon show developmental delays and intellectual disability. There is no cure or effective treatment for this rare genetic disease, but new research suggests a potential path to one. </p> <p>Researchers at the ӳý and The Jackson Laboratory have used prime editing, a precise and versatile form of gene editing, to correct the root cause of AHC in mice. The team used a scalable approach to develop prime editing treatments that directly repaired five different AHC-causing genetic mutations. Mice that received the treatment had far fewer and less severe symptoms of AHC, and survived more than twice as long as untreated mice. </p> <p>The new study, published in <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank"><em>Cell</em></a>, is the first time prime editing has been used to treat a neurological disease in animals, offering hope for treating people with AHC and other genetic brain disorders. <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">Prime editing was developed in 2019</a> by the lab of <a href="/bios/david-liu">David Liu</a>, a ӳý core institute member and co-senior author of the new paper. The technology has already been successfully tested in a clinical trial for another rare genetic disease.</p> <p>“This study is an important milestone for prime editing and one of the most exciting examples of therapeutic gene editing to come from our team,” said Liu, Richard Merkin Professor and director of the <a href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute of Transformative Technologies in Healthcare at the ӳý</a>. “It opens the door to one day repairing the underlying genetic causes of many neurological disorders that have long been considered untreatable.” Liu is also a Howard Hughes Medical Institute investigator and a professor at Harvard University.</p> <p>The ability to precisely edit DNA directly in the brain has important implications for neurological diseases, said Cathleen Lutz, vice president of the Rare Disease Translational Center at The Jackson Laboratory and co-senior author of the study. “This level of editing efficiency in the brain is really quite remarkable.”</p> <p>The team’s patient partner is RARE Hope (formerly Hope for Annabel), a non-profit focused on accelerating research on AHC and developing scalable, patient-centric research platforms to benefit the larger rare disease community. RARE Hope initiated the collaboration and was closely engaged throughout the project. </p> <p>“This study is a win not just for our community but for all rare neurological conditions, and a breakthrough moment in expanding access to a broader cohort of potential patients,” said Nina Frost, founder and president of RARE Hope, a co-author of the study, and mother of a daughter with AHC. “It’s been a privilege to collaborate on such a scientifically significant effort with a team that has kept patients at the center of proof-of-concept research — engaging the patient community, modeling the patient experience, and integrating patient priorities into experimental design. This is a model for patient-relevant, patient-centered research because the team included us as true partners.”</p> <h2>Brain gene editing</h2> <p>The vast majority of AHC cases are caused by one of four mutations in <em>ATP1A3</em>, a gene essential for brain cell function. In the new work, Liu’s team set out to simultaneously develop prime editing treatments that could fix five <em>ATP1A3 </em>mutations, including the four most common — a scale rarely attempted in therapeutic gene editing research. Most other gene editing treatments, such as <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic">one recently used to treat baby KJ Muldoon</a>, are designed to correct one mutation at a time. The scientists worked on correcting all five mutations, streamlining experiments, saving resources, and testing the robustness of the underlying science.</p> <p>“We developed a robust framework to correct multiple mutations in parallel,” said Alexander Sousa, a postdoctoral fellow in the Liu lab and one of three co-first authors along with Holt Sakai of the Liu lab and Markus Terrey of The Jackson Laboratory. “This effort was really about creating a blueprint that could be rapidly applied to other rare diseases too.”</p> <p>The researchers first tested their strategies in cultured cells from patients with AHC. They demonstrated that they could correctly repair AHC mutations in up to 90 percent of treated cells, with minimal changes to other stretches of DNA. </p> <p>Next, the group collaborated with Jackson Lab researchers to test their treatments in two mouse models of AHC, which carry <em>Atp1a3 </em>mutations similar to those in patients with AHC. Without treatment, the mice developed seizures, movement problems, and died prematurely. When the scientists injected their editing system into the brains of the animals, their symptoms disappeared or were substantially reduced. Treated mice survived more than twice as long as untreated animals. Moreover, the function of their Atp1a3 protein was restored in the brain, and their motor and cognitive deficits were ameliorated. The scientists delivered the prime editors to cells in mice using clinically validated viruses called AAVs, which are already used in FDA-approved gene therapies targeting brain cells.</p> <p>“The results really exceeded our expectations,” said Sakai. “It was incredibly exciting to see that data.”</p> <p>The team also tested traditional gene therapy, which delivered an extra, healthy copy of the <em>ATP1A3 </em>gene to cells, and found that symptoms did not improve in animals. This finding highlights the unique advantage of using gene editing to directly correct a mutation that results in a malfunctioning, disease-causing protein, the researchers said. </p> <p>“Before this study, we didn’t even know if we could intervene in AHC after birth in an animal,” said Sousa. “Now we know you can.”</p> <h2>A template for rare diseases</h2> <p>Because the treatment required direct injection into the brain shortly after birth, the team is now exploring less invasive delivery methods, and whether treatment later in life could still be effective. </p> <p>Beyond AHC, the team sees their approach as a template for tackling other rare genetic diseases — especially those that affect the brain. With the ability to rapidly design and test multiple gene editing treatments at once, they hope to bring the same precision and speed to many other conditions.</p> <p>“This is a powerful proof of concept,” said Sakai. “It shows that we can use prime editing to treat genetic brain diseases, and it lays the groundwork for translating this approach to the clinic.”<br>  </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>Support for the study was provided by the National Institutes of Health, the Chan-Zuckerberg Initiative, RARE Hope, the Alternating Hemiplegia of Childhood Foundation, the For Henry AHC Foundation, the Davis Family Foundation, the Toolbox Foundation L2C Initiative, the Cure AHC Foundation, the Howard Hughes Medical Institute, and the National Science 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>Sousa AA, Terrey M, Sakai HA et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank">In vivo prime editing rescues alternating hemiplegia of childhood in mice</a>. <em>Cell</em>. Online July 21, 2025. DOI: 10.1016/j.cell.2025.06.038</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/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, 17 Aug 2023 13:27:18 +0000 Corie Lok 1282671 at Low oxygen levels restore balance and coordination in a mouse model of a movement disorder /news/low-oxygen-levels-restore-balance-and-coordination-mouse-model-movement-disorder <span class="field field--name-title field--type-string field--label-hidden"><h1>Prime editing treats childhood brain disease in mice</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Corie Lok</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-07-21T11:37:05-04:00" class="datetime">July 21, 2025</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>Prime editing treats childhood brain disease in mice</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>Scientists use a precise form of gene editing called prime editing to correct the most common genetic mutations that cause alternating hemiplegia of childhood, a rare and severe neurological disorder that begins in infancy.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Sarah C.P. Williams </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="2025-07-21T11:37:05-04:00" title="Monday, July 21, 2025 - 11:37" class="datetime">July 21, 2025</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> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=4v-1bgTe 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=vcca1mnQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=EgQptYlI 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9" 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" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Kathleen Sweadner, Christine Simmons, and Alfred George </div> <div class="media-caption__description"> Scientists studied cultured human neurons, shown here under a microscope, that have a protein (green) with a mutation that causes alternating hemiplegia of childhood. </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/619/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 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srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=ffrhaQKJ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj" alt="Susanna Hamilton, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Next generation prime editing systems move closer to possible therapeutic applications</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>By the time they are a few months old, infants born with alternating hemiplegia of childhood (AHC) begin experiencing terrifying episodes of paralysis and seizures, and will soon show developmental delays and intellectual disability. There is no cure or effective treatment for this rare genetic disease, but new research suggests a potential path to one. </p> <p>Researchers at the ӳý and The Jackson Laboratory have used prime editing, a precise and versatile form of gene editing, to correct the root cause of AHC in mice. The team used a scalable approach to develop prime editing treatments that directly repaired five different AHC-causing genetic mutations. Mice that received the treatment had far fewer and less severe symptoms of AHC, and survived more than twice as long as untreated mice. </p> <p>The new study, published in <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank"><em>Cell</em></a>, is the first time prime editing has been used to treat a neurological disease in animals, offering hope for treating people with AHC and other genetic brain disorders. <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">Prime editing was developed in 2019</a> by the lab of <a href="/bios/david-liu">David Liu</a>, a ӳý core institute member and co-senior author of the new paper. The technology has already been successfully tested in a clinical trial for another rare genetic disease.</p> <p>“This study is an important milestone for prime editing and one of the most exciting examples of therapeutic gene editing to come from our team,” said Liu, Richard Merkin Professor and director of the <a href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute of Transformative Technologies in Healthcare at the ӳý</a>. “It opens the door to one day repairing the underlying genetic causes of many neurological disorders that have long been considered untreatable.” Liu is also a Howard Hughes Medical Institute investigator and a professor at Harvard University.</p> <p>The ability to precisely edit DNA directly in the brain has important implications for neurological diseases, said Cathleen Lutz, vice president of the Rare Disease Translational Center at The Jackson Laboratory and co-senior author of the study. “This level of editing efficiency in the brain is really quite remarkable.”</p> <p>The team’s patient partner is RARE Hope (formerly Hope for Annabel), a non-profit focused on accelerating research on AHC and developing scalable, patient-centric research platforms to benefit the larger rare disease community. RARE Hope initiated the collaboration and was closely engaged throughout the project. </p> <p>“This study is a win not just for our community but for all rare neurological conditions, and a breakthrough moment in expanding access to a broader cohort of potential patients,” said Nina Frost, founder and president of RARE Hope, a co-author of the study, and mother of a daughter with AHC. “It’s been a privilege to collaborate on such a scientifically significant effort with a team that has kept patients at the center of proof-of-concept research — engaging the patient community, modeling the patient experience, and integrating patient priorities into experimental design. This is a model for patient-relevant, patient-centered research because the team included us as true partners.”</p> <h2>Brain gene editing</h2> <p>The vast majority of AHC cases are caused by one of four mutations in <em>ATP1A3</em>, a gene essential for brain cell function. In the new work, Liu’s team set out to simultaneously develop prime editing treatments that could fix five <em>ATP1A3 </em>mutations, including the four most common — a scale rarely attempted in therapeutic gene editing research. Most other gene editing treatments, such as <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic">one recently used to treat baby KJ Muldoon</a>, are designed to correct one mutation at a time. The scientists worked on correcting all five mutations, streamlining experiments, saving resources, and testing the robustness of the underlying science.</p> <p>“We developed a robust framework to correct multiple mutations in parallel,” said Alexander Sousa, a postdoctoral fellow in the Liu lab and one of three co-first authors along with Holt Sakai of the Liu lab and Markus Terrey of The Jackson Laboratory. “This effort was really about creating a blueprint that could be rapidly applied to other rare diseases too.”</p> <p>The researchers first tested their strategies in cultured cells from patients with AHC. They demonstrated that they could correctly repair AHC mutations in up to 90 percent of treated cells, with minimal changes to other stretches of DNA. </p> <p>Next, the group collaborated with Jackson Lab researchers to test their treatments in two mouse models of AHC, which carry <em>Atp1a3 </em>mutations similar to those in patients with AHC. Without treatment, the mice developed seizures, movement problems, and died prematurely. When the scientists injected their editing system into the brains of the animals, their symptoms disappeared or were substantially reduced. Treated mice survived more than twice as long as untreated animals. Moreover, the function of their Atp1a3 protein was restored in the brain, and their motor and cognitive deficits were ameliorated. The scientists delivered the prime editors to cells in mice using clinically validated viruses called AAVs, which are already used in FDA-approved gene therapies targeting brain cells.</p> <p>“The results really exceeded our expectations,” said Sakai. “It was incredibly exciting to see that data.”</p> <p>The team also tested traditional gene therapy, which delivered an extra, healthy copy of the <em>ATP1A3 </em>gene to cells, and found that symptoms did not improve in animals. This finding highlights the unique advantage of using gene editing to directly correct a mutation that results in a malfunctioning, disease-causing protein, the researchers said. </p> <p>“Before this study, we didn’t even know if we could intervene in AHC after birth in an animal,” said Sousa. “Now we know you can.”</p> <h2>A template for rare diseases</h2> <p>Because the treatment required direct injection into the brain shortly after birth, the team is now exploring less invasive delivery methods, and whether treatment later in life could still be effective. </p> <p>Beyond AHC, the team sees their approach as a template for tackling other rare genetic diseases — especially those that affect the brain. With the ability to rapidly design and test multiple gene editing treatments at once, they hope to bring the same precision and speed to many other conditions.</p> <p>“This is a powerful proof of concept,” said Sakai. “It shows that we can use prime editing to treat genetic brain diseases, and it lays the groundwork for translating this approach to the clinic.”<br>  </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>Support for the study was provided by the National Institutes of Health, the Chan-Zuckerberg Initiative, RARE Hope, the Alternating Hemiplegia of Childhood Foundation, the For Henry AHC Foundation, the Davis Family Foundation, the Toolbox Foundation L2C Initiative, the Cure AHC Foundation, the Howard Hughes Medical Institute, and the National Science 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>Sousa AA, Terrey M, Sakai HA et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank">In vivo prime editing rescues alternating hemiplegia of childhood in mice</a>. <em>Cell</em>. Online July 21, 2025. DOI: 10.1016/j.cell.2025.06.038</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/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, 21 Jun 2023 16:58:24 +0000 adicorat 1282381 at Blood stem cells are susceptible to ferroptosis, a type of cell death /news/blood-stem-cells-are-susceptible-ferroptosis-type-cell-death <span class="field field--name-title field--type-string field--label-hidden"><h1>Prime editing treats childhood brain disease in mice</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Corie Lok</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-07-21T11:37:05-04:00" class="datetime">July 21, 2025</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>Prime editing treats childhood brain disease in mice</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>Scientists use a precise form of gene editing called prime editing to correct the most common genetic mutations that cause alternating hemiplegia of childhood, a rare and severe neurological disorder that begins in infancy.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Sarah C.P. Williams </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="2025-07-21T11:37:05-04:00" title="Monday, July 21, 2025 - 11:37" class="datetime">July 21, 2025</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> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=4v-1bgTe 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=vcca1mnQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=EgQptYlI 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9" 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" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Kathleen Sweadner, Christine Simmons, and Alfred George </div> <div class="media-caption__description"> Scientists studied cultured human neurons, shown here under a microscope, that have a protein (green) with a mutation that causes alternating hemiplegia of childhood. </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/619/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 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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-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>Related news</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/prime-editing-efficiently-corrects-cystic-fibrosis-mutation-human-lung-cells" class="node"> <div class="field field--name-field-image 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srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/longstory/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=o0ilCOx1 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/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=_VAtunv8 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/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=HMplbY8o 1x" media="all and (max-width: 539px)" type="image/png" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/longstory/News_Lui-genome-editing_news_0624_v2.png?h=d3e04ee7&itok=HMplbY8o" alt="Graphic displaying a green protein filling a gap in railroad tracks that are colored like DNA." title="Graphic displaying a green protein filling a gap in railroad tracks that are colored like DNA." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/improved-prime-editing-system-makes-gene-sized-edits-human-cells-therapeutic-levels" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Improved prime editing system makes gene-sized edits in human cells at therapeutic levels</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/new-prime-editing-system-inserts-entire-genes-human-cells" 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"> <a href="/news/new-prime-editing-system-inserts-entire-genes-human-cells"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/TwinPE-07.jpg?h=9423a5c0&itok=hCpTpO4i 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=hCpTpO4i 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=JBB_oOB9 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=JBB_oOB9 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=XOGiyqIC 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=l-wsLX11 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/TwinPE-07.jpg?h=9423a5c0&itok=l-wsLX11" alt="Ricardo Job-Reese, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/new-prime-editing-system-inserts-entire-genes-human-cells" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">New prime editing system inserts entire genes in human cells</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" 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"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=fsX83WkZ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=ffrhaQKJ 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/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj" alt="Susanna Hamilton, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Next generation prime editing systems move closer to possible therapeutic applications</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>By the time they are a few months old, infants born with alternating hemiplegia of childhood (AHC) begin experiencing terrifying episodes of paralysis and seizures, and will soon show developmental delays and intellectual disability. There is no cure or effective treatment for this rare genetic disease, but new research suggests a potential path to one. </p> <p>Researchers at the ӳý and The Jackson Laboratory have used prime editing, a precise and versatile form of gene editing, to correct the root cause of AHC in mice. The team used a scalable approach to develop prime editing treatments that directly repaired five different AHC-causing genetic mutations. Mice that received the treatment had far fewer and less severe symptoms of AHC, and survived more than twice as long as untreated mice. </p> <p>The new study, published in <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank"><em>Cell</em></a>, is the first time prime editing has been used to treat a neurological disease in animals, offering hope for treating people with AHC and other genetic brain disorders. <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">Prime editing was developed in 2019</a> by the lab of <a href="/bios/david-liu">David Liu</a>, a ӳý core institute member and co-senior author of the new paper. The technology has already been successfully tested in a clinical trial for another rare genetic disease.</p> <p>“This study is an important milestone for prime editing and one of the most exciting examples of therapeutic gene editing to come from our team,” said Liu, Richard Merkin Professor and director of the <a href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute of Transformative Technologies in Healthcare at the ӳý</a>. “It opens the door to one day repairing the underlying genetic causes of many neurological disorders that have long been considered untreatable.” Liu is also a Howard Hughes Medical Institute investigator and a professor at Harvard University.</p> <p>The ability to precisely edit DNA directly in the brain has important implications for neurological diseases, said Cathleen Lutz, vice president of the Rare Disease Translational Center at The Jackson Laboratory and co-senior author of the study. “This level of editing efficiency in the brain is really quite remarkable.”</p> <p>The team’s patient partner is RARE Hope (formerly Hope for Annabel), a non-profit focused on accelerating research on AHC and developing scalable, patient-centric research platforms to benefit the larger rare disease community. RARE Hope initiated the collaboration and was closely engaged throughout the project. </p> <p>“This study is a win not just for our community but for all rare neurological conditions, and a breakthrough moment in expanding access to a broader cohort of potential patients,” said Nina Frost, founder and president of RARE Hope, a co-author of the study, and mother of a daughter with AHC. “It’s been a privilege to collaborate on such a scientifically significant effort with a team that has kept patients at the center of proof-of-concept research — engaging the patient community, modeling the patient experience, and integrating patient priorities into experimental design. This is a model for patient-relevant, patient-centered research because the team included us as true partners.”</p> <h2>Brain gene editing</h2> <p>The vast majority of AHC cases are caused by one of four mutations in <em>ATP1A3</em>, a gene essential for brain cell function. In the new work, Liu’s team set out to simultaneously develop prime editing treatments that could fix five <em>ATP1A3 </em>mutations, including the four most common — a scale rarely attempted in therapeutic gene editing research. Most other gene editing treatments, such as <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic">one recently used to treat baby KJ Muldoon</a>, are designed to correct one mutation at a time. The scientists worked on correcting all five mutations, streamlining experiments, saving resources, and testing the robustness of the underlying science.</p> <p>“We developed a robust framework to correct multiple mutations in parallel,” said Alexander Sousa, a postdoctoral fellow in the Liu lab and one of three co-first authors along with Holt Sakai of the Liu lab and Markus Terrey of The Jackson Laboratory. “This effort was really about creating a blueprint that could be rapidly applied to other rare diseases too.”</p> <p>The researchers first tested their strategies in cultured cells from patients with AHC. They demonstrated that they could correctly repair AHC mutations in up to 90 percent of treated cells, with minimal changes to other stretches of DNA. </p> <p>Next, the group collaborated with Jackson Lab researchers to test their treatments in two mouse models of AHC, which carry <em>Atp1a3 </em>mutations similar to those in patients with AHC. Without treatment, the mice developed seizures, movement problems, and died prematurely. When the scientists injected their editing system into the brains of the animals, their symptoms disappeared or were substantially reduced. Treated mice survived more than twice as long as untreated animals. Moreover, the function of their Atp1a3 protein was restored in the brain, and their motor and cognitive deficits were ameliorated. The scientists delivered the prime editors to cells in mice using clinically validated viruses called AAVs, which are already used in FDA-approved gene therapies targeting brain cells.</p> <p>“The results really exceeded our expectations,” said Sakai. “It was incredibly exciting to see that data.”</p> <p>The team also tested traditional gene therapy, which delivered an extra, healthy copy of the <em>ATP1A3 </em>gene to cells, and found that symptoms did not improve in animals. This finding highlights the unique advantage of using gene editing to directly correct a mutation that results in a malfunctioning, disease-causing protein, the researchers said. </p> <p>“Before this study, we didn’t even know if we could intervene in AHC after birth in an animal,” said Sousa. “Now we know you can.”</p> <h2>A template for rare diseases</h2> <p>Because the treatment required direct injection into the brain shortly after birth, the team is now exploring less invasive delivery methods, and whether treatment later in life could still be effective. </p> <p>Beyond AHC, the team sees their approach as a template for tackling other rare genetic diseases — especially those that affect the brain. With the ability to rapidly design and test multiple gene editing treatments at once, they hope to bring the same precision and speed to many other conditions.</p> <p>“This is a powerful proof of concept,” said Sakai. “It shows that we can use prime editing to treat genetic brain diseases, and it lays the groundwork for translating this approach to the clinic.”<br>  </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>Support for the study was provided by the National Institutes of Health, the Chan-Zuckerberg Initiative, RARE Hope, the Alternating Hemiplegia of Childhood Foundation, the For Henry AHC Foundation, the Davis Family Foundation, the Toolbox Foundation L2C Initiative, the Cure AHC Foundation, the Howard Hughes Medical Institute, and the National Science 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>Sousa AA, Terrey M, Sakai HA et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank">In vivo prime editing rescues alternating hemiplegia of childhood in mice</a>. <em>Cell</em>. Online July 21, 2025. DOI: 10.1016/j.cell.2025.06.038</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/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, 16 Feb 2023 16:00:00 +0000 adicorat 1281686 at Gene-delivering viruses reach the brain in a step toward gene therapy for neurological diseases /news/gene-delivering-viruses-reach-brain-step-toward-gene-therapy-neurological-diseases <span class="field field--name-title field--type-string field--label-hidden"><h1>Prime editing treats childhood brain disease in mice</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Corie Lok</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-07-21T11:37:05-04:00" class="datetime">July 21, 2025</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>Prime editing treats childhood brain disease in mice</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>Scientists use a precise form of gene editing called prime editing to correct the most common genetic mutations that cause alternating hemiplegia of childhood, a rare and severe neurological disorder that begins in infancy.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Sarah C.P. Williams </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="2025-07-21T11:37:05-04:00" title="Monday, July 21, 2025 - 11:37" class="datetime">July 21, 2025</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> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=gjrfhiru 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=4v-1bgTe 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=vcca1mnQ 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=EgQptYlI 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9 1x" media="all and (max-width: 539px)" type="image/jpeg" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/ATP1A3%20mutant%20iPSC%20neurons%20AHC%20model.jpg?h=dbc6d25a&itok=hKhhCtH9" 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" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Kathleen Sweadner, Christine Simmons, and Alfred George </div> <div class="media-caption__description"> Scientists studied cultured human neurons, shown here under a microscope, that have a protein (green) with a mutation that causes alternating hemiplegia of childhood. </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/619/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 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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-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>Related news</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/prime-editing-efficiently-corrects-cystic-fibrosis-mutation-human-lung-cells" class="node"> <div class="field field--name-field-image 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type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2021/TwinPE-07.jpg?h=9423a5c0&itok=XOGiyqIC 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/2021/TwinPE-07.jpg?h=9423a5c0&itok=l-wsLX11 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/TwinPE-07.jpg?h=9423a5c0&itok=l-wsLX11" alt="Ricardo Job-Reese, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/new-prime-editing-system-inserts-entire-genes-human-cells" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">New prime editing system inserts entire genes in human cells</span> </a> </div> </article> </div> <div class="field__item"><article about="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" 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"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=kxbhcJF3 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source 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srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2021/Liu_main_v2.jpg?h=9423a5c0&itok=U9RFpxAj" alt="Susanna Hamilton, ӳý Communications" typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/next-generation-prime-editing-systems-move-closer-possible-therapeutic-applications" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Next generation prime editing systems move closer to possible therapeutic applications</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>By the time they are a few months old, infants born with alternating hemiplegia of childhood (AHC) begin experiencing terrifying episodes of paralysis and seizures, and will soon show developmental delays and intellectual disability. There is no cure or effective treatment for this rare genetic disease, but new research suggests a potential path to one. </p> <p>Researchers at the ӳý and The Jackson Laboratory have used prime editing, a precise and versatile form of gene editing, to correct the root cause of AHC in mice. The team used a scalable approach to develop prime editing treatments that directly repaired five different AHC-causing genetic mutations. Mice that received the treatment had far fewer and less severe symptoms of AHC, and survived more than twice as long as untreated mice. </p> <p>The new study, published in <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank"><em>Cell</em></a>, is the first time prime editing has been used to treat a neurological disease in animals, offering hope for treating people with AHC and other genetic brain disorders. <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">Prime editing was developed in 2019</a> by the lab of <a href="/bios/david-liu">David Liu</a>, a ӳý core institute member and co-senior author of the new paper. The technology has already been successfully tested in a clinical trial for another rare genetic disease.</p> <p>“This study is an important milestone for prime editing and one of the most exciting examples of therapeutic gene editing to come from our team,” said Liu, Richard Merkin Professor and director of the <a href="/merkin-institute-transformative-technologies-healthcare">Merkin Institute of Transformative Technologies in Healthcare at the ӳý</a>. “It opens the door to one day repairing the underlying genetic causes of many neurological disorders that have long been considered untreatable.” Liu is also a Howard Hughes Medical Institute investigator and a professor at Harvard University.</p> <p>The ability to precisely edit DNA directly in the brain has important implications for neurological diseases, said Cathleen Lutz, vice president of the Rare Disease Translational Center at The Jackson Laboratory and co-senior author of the study. “This level of editing efficiency in the brain is really quite remarkable.”</p> <p>The team’s patient partner is RARE Hope (formerly Hope for Annabel), a non-profit focused on accelerating research on AHC and developing scalable, patient-centric research platforms to benefit the larger rare disease community. RARE Hope initiated the collaboration and was closely engaged throughout the project. </p> <p>“This study is a win not just for our community but for all rare neurological conditions, and a breakthrough moment in expanding access to a broader cohort of potential patients,” said Nina Frost, founder and president of RARE Hope, a co-author of the study, and mother of a daughter with AHC. “It’s been a privilege to collaborate on such a scientifically significant effort with a team that has kept patients at the center of proof-of-concept research — engaging the patient community, modeling the patient experience, and integrating patient priorities into experimental design. This is a model for patient-relevant, patient-centered research because the team included us as true partners.”</p> <h2>Brain gene editing</h2> <p>The vast majority of AHC cases are caused by one of four mutations in <em>ATP1A3</em>, a gene essential for brain cell function. In the new work, Liu’s team set out to simultaneously develop prime editing treatments that could fix five <em>ATP1A3 </em>mutations, including the four most common — a scale rarely attempted in therapeutic gene editing research. Most other gene editing treatments, such as <a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic">one recently used to treat baby KJ Muldoon</a>, are designed to correct one mutation at a time. The scientists worked on correcting all five mutations, streamlining experiments, saving resources, and testing the robustness of the underlying science.</p> <p>“We developed a robust framework to correct multiple mutations in parallel,” said Alexander Sousa, a postdoctoral fellow in the Liu lab and one of three co-first authors along with Holt Sakai of the Liu lab and Markus Terrey of The Jackson Laboratory. “This effort was really about creating a blueprint that could be rapidly applied to other rare diseases too.”</p> <p>The researchers first tested their strategies in cultured cells from patients with AHC. They demonstrated that they could correctly repair AHC mutations in up to 90 percent of treated cells, with minimal changes to other stretches of DNA. </p> <p>Next, the group collaborated with Jackson Lab researchers to test their treatments in two mouse models of AHC, which carry <em>Atp1a3 </em>mutations similar to those in patients with AHC. Without treatment, the mice developed seizures, movement problems, and died prematurely. When the scientists injected their editing system into the brains of the animals, their symptoms disappeared or were substantially reduced. Treated mice survived more than twice as long as untreated animals. Moreover, the function of their Atp1a3 protein was restored in the brain, and their motor and cognitive deficits were ameliorated. The scientists delivered the prime editors to cells in mice using clinically validated viruses called AAVs, which are already used in FDA-approved gene therapies targeting brain cells.</p> <p>“The results really exceeded our expectations,” said Sakai. “It was incredibly exciting to see that data.”</p> <p>The team also tested traditional gene therapy, which delivered an extra, healthy copy of the <em>ATP1A3 </em>gene to cells, and found that symptoms did not improve in animals. This finding highlights the unique advantage of using gene editing to directly correct a mutation that results in a malfunctioning, disease-causing protein, the researchers said. </p> <p>“Before this study, we didn’t even know if we could intervene in AHC after birth in an animal,” said Sousa. “Now we know you can.”</p> <h2>A template for rare diseases</h2> <p>Because the treatment required direct injection into the brain shortly after birth, the team is now exploring less invasive delivery methods, and whether treatment later in life could still be effective. </p> <p>Beyond AHC, the team sees their approach as a template for tackling other rare genetic diseases — especially those that affect the brain. With the ability to rapidly design and test multiple gene editing treatments at once, they hope to bring the same precision and speed to many other conditions.</p> <p>“This is a powerful proof of concept,” said Sakai. “It shows that we can use prime editing to treat genetic brain diseases, and it lays the groundwork for translating this approach to the clinic.”<br>  </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>Support for the study was provided by the National Institutes of Health, the Chan-Zuckerberg Initiative, RARE Hope, the Alternating Hemiplegia of Childhood Foundation, the For Henry AHC Foundation, the Davis Family Foundation, the Toolbox Foundation L2C Initiative, the Cure AHC Foundation, the Howard Hughes Medical Institute, and the National Science 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>Sousa AA, Terrey M, Sakai HA et al. <a href="https://www.cell.com/cell/fulltext/S0092-8674(25)00740-8" target="_blank">In vivo prime editing rescues alternating hemiplegia of childhood in mice</a>. <em>Cell</em>. Online July 21, 2025. DOI: 10.1016/j.cell.2025.06.038</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/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, 22 Nov 2022 23:54:31 +0000 aviveros@broadinstitute.org 1262191 at