/ en Wed, 19 Nov 25 12:01:34 -0500 /news/single-prime-editing-system-could-potentially-treat-multiple-genetic-diseases <span class="field field--name-title field--type-string field--label-hidden"><h1>Single prime editing system could potentially treat multiple genetic diseases</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Karen Zusi-Tran</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-11-19T12:01:34-05:00" class="datetime">November 19, 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>Single prime editing system could potentially treat multiple genetic diseases</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>Researchers have developed a genome-editing strategy that targets a common cause of roughly 30 percent of rare diseases and could vastly improve access to gene-editing treatments for patients.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Karen Zusi-Tran </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="2025-11-19T12:01:34-05:00" title="Wednesday, November 19, 2025 - 12:01" class="datetime">November 19, 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 role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DSs035QC 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=UTVl6XHv 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=2GnfN8NZ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Agnieszka Grosso, ӳ����ý Communications </div> <div class="media-caption__description"> A single prime editing system could potentially treat multiple genetic diseases. </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/2411/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2411/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2411/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="font-family:Open Sans;background-color:#f3f3f3;padding:2em;margin-bottom:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">The new prime editing strategy addresses “nonsense mutations,” a class of mutations that halt protein production too early and can cause about one-third of genetic diseases. </li> <li aria-level="1">David Liu and his team showed that their strategy restores protein production and function in cell and animal models of four different rare diseases.</li> <li aria-level="1">This approach could streamline the development of gene-editing medicines that benefit many patients with nonsense mutations, regardless of their specific disease.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells" target="_blank">New CRISPR genome editing system offers a wide range of versatility in human cells</a></div> <div class="field__item"><a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" target="_blank">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</a></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>A team of researchers at the ӳ����ý, led by gene-editing pioneer <a href="/bios/david-liu">David Liu</a>, has developed a new genome-editing strategy that could potentially lead to a one-time treatment for multiple unrelated genetic diseases.</p> <p>Gene-editing medicines are often made one at a time to treat a specific mutation, an approach that’s difficult to scale up to address the thousands of rare diseases affecting patients around the world. The new technology, called PERT (prime editing-mediated readthrough of premature termination codons), is designed to maximize the potential of gene editing by using just one editing agent to serve as many patients as possible.</p> <p>“We're excited by the possibility that you could develop a single editing agent into a drug that may help many different types of patients, circumventing the need to invest multiple years and millions of dollars to develop each new genetic medicine for each individual,” said Liu, a core institute member, the Richard Merkin Professor, and director of the Merkin Institute for Transformative Technologies in Healthcare at ӳ����ý, the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>PERT uses prime editing — a versatile and precise DNA editing system <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">developed by Liu’s lab</a> in 2019 — to rescue a type of mutation that can cause about a third of rare diseases. These “nonsense mutations” can appear in many different genes and cause cells to stop synthesizing their associated proteins too early, resulting in truncated, malfunctioning molecules that lead to disease. Among the 200,000 disease-causing mutations documented in the ClinVar database, 24 percent are nonsense mutations.</p> <p>The PERT approach does not directly edit these nonsense mutations — a strategy that would require developing a different editing agent for each mutation — but instead makes another edit that equips cells with a tool to produce the normal, functional version of the protein, regardless of which gene is impacted.</p> <p>In a paper published in <a href="https://www.nature.com/articles/s41586-025-09732-2"><em>Nature</em></a>, the team described how they tested PERT in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1, and in a mouse model of Hurler syndrome. The technology restored protein production and alleviated disease symptoms, with no detected off-target edits, changes in normal RNA or protein production, or toxicity to the cells.</p> <p>The work was spearheaded by co-first authors Sarah Pierce and Steven Erwood, both postdoctoral associates in the Liu lab.</p> <h2>A creative solution</h2> <p>Liu and his lab have been developing new DNA-editing tools to address genetic diseases for many years. However, after seeing how challenging and resource-intensive it is for these technologies to reach patients, Liu began thinking about opportunities to streamline the process.</p> <p>“In some cases, the bottlenecks in genetic medicine aren’t the science anymore,” he said. “They’re in meeting regulatory requirements, in the manufacturing costs associated with these treatments, and in the commercial challenges of drugs that treat very small numbers of patients. Witnessing gene-editing companies make the gut-wrenching decisions of which targets to pursue — synonymous with the gut-wrenching decisions of which patients are left behind — made it clear that we need creative scientific ways to help address some of these problems.”</p> <p>The team found a potential solution by identifying a common cause of many different genetic diseases. Normally, when a cell needs to make a protein, it first transcribes DNA into mRNA. Other molecules called tRNAs then read the mRNA sequence and bring the corresponding amino acid building blocks together into a chain that becomes the final protein. A special three-letter sequence in the mRNA — UAA, UAG, or UGA — marks the end of the protein assembly instructions. This signal is called a termination codon.</p> <p>But roughly 30 percent of genetic diseases are caused by DNA mutations that create an errant termination codon somewhere in the middle of the mRNA sequence, signaling the cell to halt protein production too early. Liu’s team sought to develop a universal way to permanently equip the cell to overcome these premature termination codons, allowing protein synthesis to continue as normal.</p> <p>“Our hope is that this type of solution could provide a single, one-time gene-editing treatment that benefits patients with different diseases caused by nonsense mutations,” said Pierce.</p> <h2>Installing a new tRNA</h2> <p>The researchers came up with a creative application of prime editing to tackle this issue. They first turned to “suppressor” tRNAs. This type of tRNA adds an amino acid building block in response to a premature termination codon, allowing the cell to continue building the protein instead of halting protein synthesis midway. </p> <p>By testing tens of thousands of tRNA variants, Pierce, Erwood, and their colleagues engineered a new, highly efficient suppressor tRNA. They then optimized a prime editing system to install this tRNA directly into the genomes of cells, replacing an existing, redundant tRNA. </p> <p>“A lot of what made this possible was simply taking advantage of how versatile prime editing is,” said Erwood. “It let us make very complex changes to a tRNA in ways we couldn’t have done otherwise. We tested thousands of different prime edits until one tRNA design finally stood out.”</p> <p>The resulting prime editor permanently equips cells with the new suppressor tRNA, which allows them to produce full-length protein regardless of which specific gene is carrying a nonsense mutation.</p> <p>The researchers used prime editing to install this new suppressor tRNA in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1. Using the same prime editing system in these different cell models, they observed enzyme activity restored at approximately 20 to 70 percent of normal levels, a level theoretically high enough to alleviate disease symptoms.</p> <p>The team also tested their strategy in a mouse model of Hurler syndrome, a lysosomal storage disorder. When the scientists analyzed tissue from the mouse brain, liver, and spleen — tissues normally impacted by the disorder — they determined that PERT had restored about 6 percent of normal enzyme activity, high enough to nearly eliminate all signs of disease.</p> <p>The researchers found that PERT did not result in detected off-target edits, and did not affect the normal synthesis of other proteins. The team speculates that PERT minimally impacts normal protein production because mammalian cells have several additional ways of supporting proper protein synthesis, and because PERT leads to only low levels of the engineered suppressor tRNA in cells.</p> <p>The team is now further optimizing PERT and testing it in a variety of animal models for different genetic diseases.</p> <p>“We hope this research will eventually pave the way for a clinical trial of PERT, and will inspire other broadly applicable, disease-agnostic gene-editing strategies,” said Liu. “If you don’t have to target one mutation at a time, the size of the patient groups that could be treated with a single drug becomes much, much larger. We hope the result will be many more patients that benefit, as well as greater incentives to develop gene-editing drugs for rare diseases.”</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>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Pierce SE, Erwood S, et al. <a href="https://www.nature.com/articles/s41586-025-09732-2" target="_blank">Prime editing-installed suppressor tRNAs for disease-agnostic genome editing</a>. <em>Nature</em>. Online November 19, 2025. DOI: 10.1038/s41586-025-09732-2.</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>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This study was funded by the National Institutes of Health, the ӳ����ý Chemical Biology and Therapeutics Science program funds, and Howard Hughes Medical Institute.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/gene-therapy" hreflang="en">Gene therapy</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Wed, 19 Nov 2025 17:01:34 +0000 kzusi@broadinstitute.org 5559721 at /news/prime-editing-treats-childhood-brain-disease-mice <span class="field field--name-title field--type-string field--label-hidden"><h1>Single prime editing system could potentially treat multiple genetic diseases</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Karen Zusi-Tran</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-11-19T12:01:34-05:00" class="datetime">November 19, 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>Single prime editing system could potentially treat multiple genetic diseases</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>Researchers have developed a genome-editing strategy that targets a common cause of roughly 30 percent of rare diseases and could vastly improve access to gene-editing treatments for patients.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Karen Zusi-Tran </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="2025-11-19T12:01:34-05:00" title="Wednesday, November 19, 2025 - 12:01" class="datetime">November 19, 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 role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DSs035QC 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=UTVl6XHv 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=2GnfN8NZ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Agnieszka Grosso, ӳ����ý Communications </div> <div class="media-caption__description"> A single prime editing system could potentially treat multiple genetic diseases. </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/2411/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button 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href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="font-family:Open Sans;background-color:#f3f3f3;padding:2em;margin-bottom:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">The new prime editing strategy addresses “nonsense mutations,” a class of mutations that halt protein production too early and can cause about one-third of genetic diseases. </li> <li aria-level="1">David Liu and his team showed that their strategy restores protein production and function in cell and animal models of four different rare diseases.</li> <li aria-level="1">This approach could streamline the development of gene-editing medicines that benefit many patients with nonsense mutations, regardless of their specific disease.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells" target="_blank">New CRISPR genome editing system offers a wide range of versatility in human cells</a></div> <div class="field__item"><a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" target="_blank">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</a></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>A team of researchers at the ӳ����ý, led by gene-editing pioneer <a href="/bios/david-liu">David Liu</a>, has developed a new genome-editing strategy that could potentially lead to a one-time treatment for multiple unrelated genetic diseases.</p> <p>Gene-editing medicines are often made one at a time to treat a specific mutation, an approach that’s difficult to scale up to address the thousands of rare diseases affecting patients around the world. The new technology, called PERT (prime editing-mediated readthrough of premature termination codons), is designed to maximize the potential of gene editing by using just one editing agent to serve as many patients as possible.</p> <p>“We're excited by the possibility that you could develop a single editing agent into a drug that may help many different types of patients, circumventing the need to invest multiple years and millions of dollars to develop each new genetic medicine for each individual,” said Liu, a core institute member, the Richard Merkin Professor, and director of the Merkin Institute for Transformative Technologies in Healthcare at ӳ����ý, the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>PERT uses prime editing — a versatile and precise DNA editing system <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">developed by Liu’s lab</a> in 2019 — to rescue a type of mutation that can cause about a third of rare diseases. These “nonsense mutations” can appear in many different genes and cause cells to stop synthesizing their associated proteins too early, resulting in truncated, malfunctioning molecules that lead to disease. Among the 200,000 disease-causing mutations documented in the ClinVar database, 24 percent are nonsense mutations.</p> <p>The PERT approach does not directly edit these nonsense mutations — a strategy that would require developing a different editing agent for each mutation — but instead makes another edit that equips cells with a tool to produce the normal, functional version of the protein, regardless of which gene is impacted.</p> <p>In a paper published in <a href="https://www.nature.com/articles/s41586-025-09732-2"><em>Nature</em></a>, the team described how they tested PERT in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1, and in a mouse model of Hurler syndrome. The technology restored protein production and alleviated disease symptoms, with no detected off-target edits, changes in normal RNA or protein production, or toxicity to the cells.</p> <p>The work was spearheaded by co-first authors Sarah Pierce and Steven Erwood, both postdoctoral associates in the Liu lab.</p> <h2>A creative solution</h2> <p>Liu and his lab have been developing new DNA-editing tools to address genetic diseases for many years. However, after seeing how challenging and resource-intensive it is for these technologies to reach patients, Liu began thinking about opportunities to streamline the process.</p> <p>“In some cases, the bottlenecks in genetic medicine aren’t the science anymore,” he said. “They’re in meeting regulatory requirements, in the manufacturing costs associated with these treatments, and in the commercial challenges of drugs that treat very small numbers of patients. Witnessing gene-editing companies make the gut-wrenching decisions of which targets to pursue — synonymous with the gut-wrenching decisions of which patients are left behind — made it clear that we need creative scientific ways to help address some of these problems.”</p> <p>The team found a potential solution by identifying a common cause of many different genetic diseases. Normally, when a cell needs to make a protein, it first transcribes DNA into mRNA. Other molecules called tRNAs then read the mRNA sequence and bring the corresponding amino acid building blocks together into a chain that becomes the final protein. A special three-letter sequence in the mRNA — UAA, UAG, or UGA — marks the end of the protein assembly instructions. This signal is called a termination codon.</p> <p>But roughly 30 percent of genetic diseases are caused by DNA mutations that create an errant termination codon somewhere in the middle of the mRNA sequence, signaling the cell to halt protein production too early. Liu’s team sought to develop a universal way to permanently equip the cell to overcome these premature termination codons, allowing protein synthesis to continue as normal.</p> <p>“Our hope is that this type of solution could provide a single, one-time gene-editing treatment that benefits patients with different diseases caused by nonsense mutations,” said Pierce.</p> <h2>Installing a new tRNA</h2> <p>The researchers came up with a creative application of prime editing to tackle this issue. They first turned to “suppressor” tRNAs. This type of tRNA adds an amino acid building block in response to a premature termination codon, allowing the cell to continue building the protein instead of halting protein synthesis midway. </p> <p>By testing tens of thousands of tRNA variants, Pierce, Erwood, and their colleagues engineered a new, highly efficient suppressor tRNA. They then optimized a prime editing system to install this tRNA directly into the genomes of cells, replacing an existing, redundant tRNA. </p> <p>“A lot of what made this possible was simply taking advantage of how versatile prime editing is,” said Erwood. “It let us make very complex changes to a tRNA in ways we couldn’t have done otherwise. We tested thousands of different prime edits until one tRNA design finally stood out.”</p> <p>The resulting prime editor permanently equips cells with the new suppressor tRNA, which allows them to produce full-length protein regardless of which specific gene is carrying a nonsense mutation.</p> <p>The researchers used prime editing to install this new suppressor tRNA in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1. Using the same prime editing system in these different cell models, they observed enzyme activity restored at approximately 20 to 70 percent of normal levels, a level theoretically high enough to alleviate disease symptoms.</p> <p>The team also tested their strategy in a mouse model of Hurler syndrome, a lysosomal storage disorder. When the scientists analyzed tissue from the mouse brain, liver, and spleen — tissues normally impacted by the disorder — they determined that PERT had restored about 6 percent of normal enzyme activity, high enough to nearly eliminate all signs of disease.</p> <p>The researchers found that PERT did not result in detected off-target edits, and did not affect the normal synthesis of other proteins. The team speculates that PERT minimally impacts normal protein production because mammalian cells have several additional ways of supporting proper protein synthesis, and because PERT leads to only low levels of the engineered suppressor tRNA in cells.</p> <p>The team is now further optimizing PERT and testing it in a variety of animal models for different genetic diseases.</p> <p>“We hope this research will eventually pave the way for a clinical trial of PERT, and will inspire other broadly applicable, disease-agnostic gene-editing strategies,” said Liu. “If you don’t have to target one mutation at a time, the size of the patient groups that could be treated with a single drug becomes much, much larger. We hope the result will be many more patients that benefit, as well as greater incentives to develop gene-editing drugs for rare diseases.”</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>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Pierce SE, Erwood S, et al. <a href="https://www.nature.com/articles/s41586-025-09732-2" target="_blank">Prime editing-installed suppressor tRNAs for disease-agnostic genome editing</a>. <em>Nature</em>. Online November 19, 2025. DOI: 10.1038/s41586-025-09732-2.</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>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This study was funded by the National Institutes of Health, the ӳ����ý Chemical Biology and Therapeutics Science program funds, and Howard Hughes Medical Institute.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/gene-therapy" hreflang="en">Gene therapy</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Mon, 21 Jul 2025 15:37:05 +0000 Corie Lok 5559001 at /news/gene-editing-disrupts-huntingtons-mutation-mice <span class="field field--name-title field--type-string field--label-hidden"><h1>Single prime editing system could potentially treat multiple genetic diseases</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Karen Zusi-Tran</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-11-19T12:01:34-05:00" class="datetime">November 19, 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>Single prime editing system could potentially treat multiple genetic diseases</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>Researchers have developed a genome-editing strategy that targets a common cause of roughly 30 percent of rare diseases and could vastly improve access to gene-editing treatments for patients.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Karen Zusi-Tran </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="2025-11-19T12:01:34-05:00" title="Wednesday, November 19, 2025 - 12:01" class="datetime">November 19, 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 role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DSs035QC 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=UTVl6XHv 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=2GnfN8NZ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Agnieszka Grosso, ӳ����ý Communications </div> <div class="media-caption__description"> A single prime editing system could potentially treat multiple genetic diseases. </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/2411/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2411/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2411/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="font-family:Open Sans;background-color:#f3f3f3;padding:2em;margin-bottom:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">The new prime editing strategy addresses “nonsense mutations,” a class of mutations that halt protein production too early and can cause about one-third of genetic diseases. </li> <li aria-level="1">David Liu and his team showed that their strategy restores protein production and function in cell and animal models of four different rare diseases.</li> <li aria-level="1">This approach could streamline the development of gene-editing medicines that benefit many patients with nonsense mutations, regardless of their specific disease.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells" target="_blank">New CRISPR genome editing system offers a wide range of versatility in human cells</a></div> <div class="field__item"><a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" target="_blank">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</a></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>A team of researchers at the ӳ����ý, led by gene-editing pioneer <a href="/bios/david-liu">David Liu</a>, has developed a new genome-editing strategy that could potentially lead to a one-time treatment for multiple unrelated genetic diseases.</p> <p>Gene-editing medicines are often made one at a time to treat a specific mutation, an approach that’s difficult to scale up to address the thousands of rare diseases affecting patients around the world. The new technology, called PERT (prime editing-mediated readthrough of premature termination codons), is designed to maximize the potential of gene editing by using just one editing agent to serve as many patients as possible.</p> <p>“We're excited by the possibility that you could develop a single editing agent into a drug that may help many different types of patients, circumventing the need to invest multiple years and millions of dollars to develop each new genetic medicine for each individual,” said Liu, a core institute member, the Richard Merkin Professor, and director of the Merkin Institute for Transformative Technologies in Healthcare at ӳ����ý, the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>PERT uses prime editing — a versatile and precise DNA editing system <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">developed by Liu’s lab</a> in 2019 — to rescue a type of mutation that can cause about a third of rare diseases. These “nonsense mutations” can appear in many different genes and cause cells to stop synthesizing their associated proteins too early, resulting in truncated, malfunctioning molecules that lead to disease. Among the 200,000 disease-causing mutations documented in the ClinVar database, 24 percent are nonsense mutations.</p> <p>The PERT approach does not directly edit these nonsense mutations — a strategy that would require developing a different editing agent for each mutation — but instead makes another edit that equips cells with a tool to produce the normal, functional version of the protein, regardless of which gene is impacted.</p> <p>In a paper published in <a href="https://www.nature.com/articles/s41586-025-09732-2"><em>Nature</em></a>, the team described how they tested PERT in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1, and in a mouse model of Hurler syndrome. The technology restored protein production and alleviated disease symptoms, with no detected off-target edits, changes in normal RNA or protein production, or toxicity to the cells.</p> <p>The work was spearheaded by co-first authors Sarah Pierce and Steven Erwood, both postdoctoral associates in the Liu lab.</p> <h2>A creative solution</h2> <p>Liu and his lab have been developing new DNA-editing tools to address genetic diseases for many years. However, after seeing how challenging and resource-intensive it is for these technologies to reach patients, Liu began thinking about opportunities to streamline the process.</p> <p>“In some cases, the bottlenecks in genetic medicine aren’t the science anymore,” he said. “They’re in meeting regulatory requirements, in the manufacturing costs associated with these treatments, and in the commercial challenges of drugs that treat very small numbers of patients. Witnessing gene-editing companies make the gut-wrenching decisions of which targets to pursue — synonymous with the gut-wrenching decisions of which patients are left behind — made it clear that we need creative scientific ways to help address some of these problems.”</p> <p>The team found a potential solution by identifying a common cause of many different genetic diseases. Normally, when a cell needs to make a protein, it first transcribes DNA into mRNA. Other molecules called tRNAs then read the mRNA sequence and bring the corresponding amino acid building blocks together into a chain that becomes the final protein. A special three-letter sequence in the mRNA — UAA, UAG, or UGA — marks the end of the protein assembly instructions. This signal is called a termination codon.</p> <p>But roughly 30 percent of genetic diseases are caused by DNA mutations that create an errant termination codon somewhere in the middle of the mRNA sequence, signaling the cell to halt protein production too early. Liu’s team sought to develop a universal way to permanently equip the cell to overcome these premature termination codons, allowing protein synthesis to continue as normal.</p> <p>“Our hope is that this type of solution could provide a single, one-time gene-editing treatment that benefits patients with different diseases caused by nonsense mutations,” said Pierce.</p> <h2>Installing a new tRNA</h2> <p>The researchers came up with a creative application of prime editing to tackle this issue. They first turned to “suppressor” tRNAs. This type of tRNA adds an amino acid building block in response to a premature termination codon, allowing the cell to continue building the protein instead of halting protein synthesis midway. </p> <p>By testing tens of thousands of tRNA variants, Pierce, Erwood, and their colleagues engineered a new, highly efficient suppressor tRNA. They then optimized a prime editing system to install this tRNA directly into the genomes of cells, replacing an existing, redundant tRNA. </p> <p>“A lot of what made this possible was simply taking advantage of how versatile prime editing is,” said Erwood. “It let us make very complex changes to a tRNA in ways we couldn’t have done otherwise. We tested thousands of different prime edits until one tRNA design finally stood out.”</p> <p>The resulting prime editor permanently equips cells with the new suppressor tRNA, which allows them to produce full-length protein regardless of which specific gene is carrying a nonsense mutation.</p> <p>The researchers used prime editing to install this new suppressor tRNA in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1. Using the same prime editing system in these different cell models, they observed enzyme activity restored at approximately 20 to 70 percent of normal levels, a level theoretically high enough to alleviate disease symptoms.</p> <p>The team also tested their strategy in a mouse model of Hurler syndrome, a lysosomal storage disorder. When the scientists analyzed tissue from the mouse brain, liver, and spleen — tissues normally impacted by the disorder — they determined that PERT had restored about 6 percent of normal enzyme activity, high enough to nearly eliminate all signs of disease.</p> <p>The researchers found that PERT did not result in detected off-target edits, and did not affect the normal synthesis of other proteins. The team speculates that PERT minimally impacts normal protein production because mammalian cells have several additional ways of supporting proper protein synthesis, and because PERT leads to only low levels of the engineered suppressor tRNA in cells.</p> <p>The team is now further optimizing PERT and testing it in a variety of animal models for different genetic diseases.</p> <p>“We hope this research will eventually pave the way for a clinical trial of PERT, and will inspire other broadly applicable, disease-agnostic gene-editing strategies,” said Liu. “If you don’t have to target one mutation at a time, the size of the patient groups that could be treated with a single drug becomes much, much larger. We hope the result will be many more patients that benefit, as well as greater incentives to develop gene-editing drugs for rare diseases.”</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>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Pierce SE, Erwood S, et al. <a href="https://www.nature.com/articles/s41586-025-09732-2" target="_blank">Prime editing-installed suppressor tRNAs for disease-agnostic genome editing</a>. <em>Nature</em>. Online November 19, 2025. DOI: 10.1038/s41586-025-09732-2.</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>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This study was funded by the National Institutes of Health, the ӳ����ý Chemical Biology and Therapeutics Science program funds, and Howard Hughes Medical Institute.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/gene-therapy" hreflang="en">Gene therapy</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Tue, 27 May 2025 13:00:00 +0000 adicorat 5558521 at /news/evolved-gene-editor-inserts-entire-genes-human-cells <span class="field field--name-title field--type-string field--label-hidden"><h1>Single prime editing system could potentially treat multiple genetic diseases</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Karen Zusi-Tran</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-11-19T12:01:34-05:00" class="datetime">November 19, 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>Single prime editing system could potentially treat multiple genetic diseases</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>Researchers have developed a genome-editing strategy that targets a common cause of roughly 30 percent of rare diseases and could vastly improve access to gene-editing treatments for patients.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Karen Zusi-Tran </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="2025-11-19T12:01:34-05:00" title="Wednesday, November 19, 2025 - 12:01" class="datetime">November 19, 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 role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DSs035QC 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=UTVl6XHv 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=2GnfN8NZ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Agnieszka Grosso, ӳ����ý Communications </div> <div class="media-caption__description"> A single prime editing system could potentially treat multiple genetic diseases. </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/2411/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2411/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2411/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="font-family:Open Sans;background-color:#f3f3f3;padding:2em;margin-bottom:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">The new prime editing strategy addresses “nonsense mutations,” a class of mutations that halt protein production too early and can cause about one-third of genetic diseases. </li> <li aria-level="1">David Liu and his team showed that their strategy restores protein production and function in cell and animal models of four different rare diseases.</li> <li aria-level="1">This approach could streamline the development of gene-editing medicines that benefit many patients with nonsense mutations, regardless of their specific disease.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells" target="_blank">New CRISPR genome editing system offers a wide range of versatility in human cells</a></div> <div class="field__item"><a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" target="_blank">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</a></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>A team of researchers at the ӳ����ý, led by gene-editing pioneer <a href="/bios/david-liu">David Liu</a>, has developed a new genome-editing strategy that could potentially lead to a one-time treatment for multiple unrelated genetic diseases.</p> <p>Gene-editing medicines are often made one at a time to treat a specific mutation, an approach that’s difficult to scale up to address the thousands of rare diseases affecting patients around the world. The new technology, called PERT (prime editing-mediated readthrough of premature termination codons), is designed to maximize the potential of gene editing by using just one editing agent to serve as many patients as possible.</p> <p>“We're excited by the possibility that you could develop a single editing agent into a drug that may help many different types of patients, circumventing the need to invest multiple years and millions of dollars to develop each new genetic medicine for each individual,” said Liu, a core institute member, the Richard Merkin Professor, and director of the Merkin Institute for Transformative Technologies in Healthcare at ӳ����ý, the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>PERT uses prime editing — a versatile and precise DNA editing system <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">developed by Liu’s lab</a> in 2019 — to rescue a type of mutation that can cause about a third of rare diseases. These “nonsense mutations” can appear in many different genes and cause cells to stop synthesizing their associated proteins too early, resulting in truncated, malfunctioning molecules that lead to disease. Among the 200,000 disease-causing mutations documented in the ClinVar database, 24 percent are nonsense mutations.</p> <p>The PERT approach does not directly edit these nonsense mutations — a strategy that would require developing a different editing agent for each mutation — but instead makes another edit that equips cells with a tool to produce the normal, functional version of the protein, regardless of which gene is impacted.</p> <p>In a paper published in <a href="https://www.nature.com/articles/s41586-025-09732-2"><em>Nature</em></a>, the team described how they tested PERT in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1, and in a mouse model of Hurler syndrome. The technology restored protein production and alleviated disease symptoms, with no detected off-target edits, changes in normal RNA or protein production, or toxicity to the cells.</p> <p>The work was spearheaded by co-first authors Sarah Pierce and Steven Erwood, both postdoctoral associates in the Liu lab.</p> <h2>A creative solution</h2> <p>Liu and his lab have been developing new DNA-editing tools to address genetic diseases for many years. However, after seeing how challenging and resource-intensive it is for these technologies to reach patients, Liu began thinking about opportunities to streamline the process.</p> <p>“In some cases, the bottlenecks in genetic medicine aren’t the science anymore,” he said. “They’re in meeting regulatory requirements, in the manufacturing costs associated with these treatments, and in the commercial challenges of drugs that treat very small numbers of patients. Witnessing gene-editing companies make the gut-wrenching decisions of which targets to pursue — synonymous with the gut-wrenching decisions of which patients are left behind — made it clear that we need creative scientific ways to help address some of these problems.”</p> <p>The team found a potential solution by identifying a common cause of many different genetic diseases. Normally, when a cell needs to make a protein, it first transcribes DNA into mRNA. Other molecules called tRNAs then read the mRNA sequence and bring the corresponding amino acid building blocks together into a chain that becomes the final protein. A special three-letter sequence in the mRNA — UAA, UAG, or UGA — marks the end of the protein assembly instructions. This signal is called a termination codon.</p> <p>But roughly 30 percent of genetic diseases are caused by DNA mutations that create an errant termination codon somewhere in the middle of the mRNA sequence, signaling the cell to halt protein production too early. Liu’s team sought to develop a universal way to permanently equip the cell to overcome these premature termination codons, allowing protein synthesis to continue as normal.</p> <p>“Our hope is that this type of solution could provide a single, one-time gene-editing treatment that benefits patients with different diseases caused by nonsense mutations,” said Pierce.</p> <h2>Installing a new tRNA</h2> <p>The researchers came up with a creative application of prime editing to tackle this issue. They first turned to “suppressor” tRNAs. This type of tRNA adds an amino acid building block in response to a premature termination codon, allowing the cell to continue building the protein instead of halting protein synthesis midway. </p> <p>By testing tens of thousands of tRNA variants, Pierce, Erwood, and their colleagues engineered a new, highly efficient suppressor tRNA. They then optimized a prime editing system to install this tRNA directly into the genomes of cells, replacing an existing, redundant tRNA. </p> <p>“A lot of what made this possible was simply taking advantage of how versatile prime editing is,” said Erwood. “It let us make very complex changes to a tRNA in ways we couldn’t have done otherwise. We tested thousands of different prime edits until one tRNA design finally stood out.”</p> <p>The resulting prime editor permanently equips cells with the new suppressor tRNA, which allows them to produce full-length protein regardless of which specific gene is carrying a nonsense mutation.</p> <p>The researchers used prime editing to install this new suppressor tRNA in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1. Using the same prime editing system in these different cell models, they observed enzyme activity restored at approximately 20 to 70 percent of normal levels, a level theoretically high enough to alleviate disease symptoms.</p> <p>The team also tested their strategy in a mouse model of Hurler syndrome, a lysosomal storage disorder. When the scientists analyzed tissue from the mouse brain, liver, and spleen — tissues normally impacted by the disorder — they determined that PERT had restored about 6 percent of normal enzyme activity, high enough to nearly eliminate all signs of disease.</p> <p>The researchers found that PERT did not result in detected off-target edits, and did not affect the normal synthesis of other proteins. The team speculates that PERT minimally impacts normal protein production because mammalian cells have several additional ways of supporting proper protein synthesis, and because PERT leads to only low levels of the engineered suppressor tRNA in cells.</p> <p>The team is now further optimizing PERT and testing it in a variety of animal models for different genetic diseases.</p> <p>“We hope this research will eventually pave the way for a clinical trial of PERT, and will inspire other broadly applicable, disease-agnostic gene-editing strategies,” said Liu. “If you don’t have to target one mutation at a time, the size of the patient groups that could be treated with a single drug becomes much, much larger. We hope the result will be many more patients that benefit, as well as greater incentives to develop gene-editing drugs for rare diseases.”</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>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Pierce SE, Erwood S, et al. <a href="https://www.nature.com/articles/s41586-025-09732-2" target="_blank">Prime editing-installed suppressor tRNAs for disease-agnostic genome editing</a>. <em>Nature</em>. Online November 19, 2025. DOI: 10.1038/s41586-025-09732-2.</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>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This study was funded by the National Institutes of Health, the ӳ����ý Chemical Biology and Therapeutics Science program funds, and Howard Hughes Medical Institute.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/gene-therapy" hreflang="en">Gene therapy</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Thu, 15 May 2025 18:00:00 +0000 adicorat 5558566 at /news/gene-editing-extends-lifespan-mouse-model-prion-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Single prime editing system could potentially treat multiple genetic diseases</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Karen Zusi-Tran</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-11-19T12:01:34-05:00" class="datetime">November 19, 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>Single prime editing system could potentially treat multiple genetic diseases</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>Researchers have developed a genome-editing strategy that targets a common cause of roughly 30 percent of rare diseases and could vastly improve access to gene-editing treatments for patients.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Karen Zusi-Tran </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="2025-11-19T12:01:34-05:00" title="Wednesday, November 19, 2025 - 12:01" class="datetime">November 19, 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 role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DSs035QC 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=UTVl6XHv 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=2GnfN8NZ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Agnieszka Grosso, ӳ����ý Communications </div> <div class="media-caption__description"> A single prime editing system could potentially treat multiple genetic diseases. </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/2411/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2411/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2411/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="font-family:Open Sans;background-color:#f3f3f3;padding:2em;margin-bottom:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">The new prime editing strategy addresses “nonsense mutations,” a class of mutations that halt protein production too early and can cause about one-third of genetic diseases. </li> <li aria-level="1">David Liu and his team showed that their strategy restores protein production and function in cell and animal models of four different rare diseases.</li> <li aria-level="1">This approach could streamline the development of gene-editing medicines that benefit many patients with nonsense mutations, regardless of their specific disease.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells" target="_blank">New CRISPR genome editing system offers a wide range of versatility in human cells</a></div> <div class="field__item"><a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" target="_blank">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</a></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>A team of researchers at the ӳ����ý, led by gene-editing pioneer <a href="/bios/david-liu">David Liu</a>, has developed a new genome-editing strategy that could potentially lead to a one-time treatment for multiple unrelated genetic diseases.</p> <p>Gene-editing medicines are often made one at a time to treat a specific mutation, an approach that’s difficult to scale up to address the thousands of rare diseases affecting patients around the world. The new technology, called PERT (prime editing-mediated readthrough of premature termination codons), is designed to maximize the potential of gene editing by using just one editing agent to serve as many patients as possible.</p> <p>“We're excited by the possibility that you could develop a single editing agent into a drug that may help many different types of patients, circumventing the need to invest multiple years and millions of dollars to develop each new genetic medicine for each individual,” said Liu, a core institute member, the Richard Merkin Professor, and director of the Merkin Institute for Transformative Technologies in Healthcare at ӳ����ý, the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>PERT uses prime editing — a versatile and precise DNA editing system <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">developed by Liu’s lab</a> in 2019 — to rescue a type of mutation that can cause about a third of rare diseases. These “nonsense mutations” can appear in many different genes and cause cells to stop synthesizing their associated proteins too early, resulting in truncated, malfunctioning molecules that lead to disease. Among the 200,000 disease-causing mutations documented in the ClinVar database, 24 percent are nonsense mutations.</p> <p>The PERT approach does not directly edit these nonsense mutations — a strategy that would require developing a different editing agent for each mutation — but instead makes another edit that equips cells with a tool to produce the normal, functional version of the protein, regardless of which gene is impacted.</p> <p>In a paper published in <a href="https://www.nature.com/articles/s41586-025-09732-2"><em>Nature</em></a>, the team described how they tested PERT in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1, and in a mouse model of Hurler syndrome. The technology restored protein production and alleviated disease symptoms, with no detected off-target edits, changes in normal RNA or protein production, or toxicity to the cells.</p> <p>The work was spearheaded by co-first authors Sarah Pierce and Steven Erwood, both postdoctoral associates in the Liu lab.</p> <h2>A creative solution</h2> <p>Liu and his lab have been developing new DNA-editing tools to address genetic diseases for many years. However, after seeing how challenging and resource-intensive it is for these technologies to reach patients, Liu began thinking about opportunities to streamline the process.</p> <p>“In some cases, the bottlenecks in genetic medicine aren’t the science anymore,” he said. “They’re in meeting regulatory requirements, in the manufacturing costs associated with these treatments, and in the commercial challenges of drugs that treat very small numbers of patients. Witnessing gene-editing companies make the gut-wrenching decisions of which targets to pursue — synonymous with the gut-wrenching decisions of which patients are left behind — made it clear that we need creative scientific ways to help address some of these problems.”</p> <p>The team found a potential solution by identifying a common cause of many different genetic diseases. Normally, when a cell needs to make a protein, it first transcribes DNA into mRNA. Other molecules called tRNAs then read the mRNA sequence and bring the corresponding amino acid building blocks together into a chain that becomes the final protein. A special three-letter sequence in the mRNA — UAA, UAG, or UGA — marks the end of the protein assembly instructions. This signal is called a termination codon.</p> <p>But roughly 30 percent of genetic diseases are caused by DNA mutations that create an errant termination codon somewhere in the middle of the mRNA sequence, signaling the cell to halt protein production too early. Liu’s team sought to develop a universal way to permanently equip the cell to overcome these premature termination codons, allowing protein synthesis to continue as normal.</p> <p>“Our hope is that this type of solution could provide a single, one-time gene-editing treatment that benefits patients with different diseases caused by nonsense mutations,” said Pierce.</p> <h2>Installing a new tRNA</h2> <p>The researchers came up with a creative application of prime editing to tackle this issue. They first turned to “suppressor” tRNAs. This type of tRNA adds an amino acid building block in response to a premature termination codon, allowing the cell to continue building the protein instead of halting protein synthesis midway. </p> <p>By testing tens of thousands of tRNA variants, Pierce, Erwood, and their colleagues engineered a new, highly efficient suppressor tRNA. They then optimized a prime editing system to install this tRNA directly into the genomes of cells, replacing an existing, redundant tRNA. </p> <p>“A lot of what made this possible was simply taking advantage of how versatile prime editing is,” said Erwood. “It let us make very complex changes to a tRNA in ways we couldn’t have done otherwise. We tested thousands of different prime edits until one tRNA design finally stood out.”</p> <p>The resulting prime editor permanently equips cells with the new suppressor tRNA, which allows them to produce full-length protein regardless of which specific gene is carrying a nonsense mutation.</p> <p>The researchers used prime editing to install this new suppressor tRNA in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1. Using the same prime editing system in these different cell models, they observed enzyme activity restored at approximately 20 to 70 percent of normal levels, a level theoretically high enough to alleviate disease symptoms.</p> <p>The team also tested their strategy in a mouse model of Hurler syndrome, a lysosomal storage disorder. When the scientists analyzed tissue from the mouse brain, liver, and spleen — tissues normally impacted by the disorder — they determined that PERT had restored about 6 percent of normal enzyme activity, high enough to nearly eliminate all signs of disease.</p> <p>The researchers found that PERT did not result in detected off-target edits, and did not affect the normal synthesis of other proteins. The team speculates that PERT minimally impacts normal protein production because mammalian cells have several additional ways of supporting proper protein synthesis, and because PERT leads to only low levels of the engineered suppressor tRNA in cells.</p> <p>The team is now further optimizing PERT and testing it in a variety of animal models for different genetic diseases.</p> <p>“We hope this research will eventually pave the way for a clinical trial of PERT, and will inspire other broadly applicable, disease-agnostic gene-editing strategies,” said Liu. “If you don’t have to target one mutation at a time, the size of the patient groups that could be treated with a single drug becomes much, much larger. We hope the result will be many more patients that benefit, as well as greater incentives to develop gene-editing drugs for rare diseases.”</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>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Pierce SE, Erwood S, et al. <a href="https://www.nature.com/articles/s41586-025-09732-2" target="_blank">Prime editing-installed suppressor tRNAs for disease-agnostic genome editing</a>. <em>Nature</em>. Online November 19, 2025. DOI: 10.1038/s41586-025-09732-2.</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>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This study was funded by the National Institutes of Health, the ӳ����ý Chemical Biology and Therapeutics Science program funds, and Howard Hughes Medical Institute.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/gene-therapy" hreflang="en">Gene therapy</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 /news/prime-editing-efficiently-corrects-cystic-fibrosis-mutation-human-lung-cells <span class="field field--name-title field--type-string field--label-hidden"><h1>Single prime editing system could potentially treat multiple genetic diseases</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Karen Zusi-Tran</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-11-19T12:01:34-05:00" class="datetime">November 19, 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>Single prime editing system could potentially treat multiple genetic diseases</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>Researchers have developed a genome-editing strategy that targets a common cause of roughly 30 percent of rare diseases and could vastly improve access to gene-editing treatments for patients.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Karen Zusi-Tran </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="2025-11-19T12:01:34-05:00" title="Wednesday, November 19, 2025 - 12:01" class="datetime">November 19, 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 role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DSs035QC 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=UTVl6XHv 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=2GnfN8NZ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Agnieszka Grosso, ӳ����ý Communications </div> <div class="media-caption__description"> A single prime editing system could potentially treat multiple genetic diseases. </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/2411/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2411/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2411/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="font-family:Open Sans;background-color:#f3f3f3;padding:2em;margin-bottom:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">The new prime editing strategy addresses “nonsense mutations,” a class of mutations that halt protein production too early and can cause about one-third of genetic diseases. </li> <li aria-level="1">David Liu and his team showed that their strategy restores protein production and function in cell and animal models of four different rare diseases.</li> <li aria-level="1">This approach could streamline the development of gene-editing medicines that benefit many patients with nonsense mutations, regardless of their specific disease.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells" target="_blank">New CRISPR genome editing system offers a wide range of versatility in human cells</a></div> <div class="field__item"><a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" target="_blank">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</a></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>A team of researchers at the ӳ����ý, led by gene-editing pioneer <a href="/bios/david-liu">David Liu</a>, has developed a new genome-editing strategy that could potentially lead to a one-time treatment for multiple unrelated genetic diseases.</p> <p>Gene-editing medicines are often made one at a time to treat a specific mutation, an approach that’s difficult to scale up to address the thousands of rare diseases affecting patients around the world. The new technology, called PERT (prime editing-mediated readthrough of premature termination codons), is designed to maximize the potential of gene editing by using just one editing agent to serve as many patients as possible.</p> <p>“We're excited by the possibility that you could develop a single editing agent into a drug that may help many different types of patients, circumventing the need to invest multiple years and millions of dollars to develop each new genetic medicine for each individual,” said Liu, a core institute member, the Richard Merkin Professor, and director of the Merkin Institute for Transformative Technologies in Healthcare at ӳ����ý, the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>PERT uses prime editing — a versatile and precise DNA editing system <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">developed by Liu’s lab</a> in 2019 — to rescue a type of mutation that can cause about a third of rare diseases. These “nonsense mutations” can appear in many different genes and cause cells to stop synthesizing their associated proteins too early, resulting in truncated, malfunctioning molecules that lead to disease. Among the 200,000 disease-causing mutations documented in the ClinVar database, 24 percent are nonsense mutations.</p> <p>The PERT approach does not directly edit these nonsense mutations — a strategy that would require developing a different editing agent for each mutation — but instead makes another edit that equips cells with a tool to produce the normal, functional version of the protein, regardless of which gene is impacted.</p> <p>In a paper published in <a href="https://www.nature.com/articles/s41586-025-09732-2"><em>Nature</em></a>, the team described how they tested PERT in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1, and in a mouse model of Hurler syndrome. The technology restored protein production and alleviated disease symptoms, with no detected off-target edits, changes in normal RNA or protein production, or toxicity to the cells.</p> <p>The work was spearheaded by co-first authors Sarah Pierce and Steven Erwood, both postdoctoral associates in the Liu lab.</p> <h2>A creative solution</h2> <p>Liu and his lab have been developing new DNA-editing tools to address genetic diseases for many years. However, after seeing how challenging and resource-intensive it is for these technologies to reach patients, Liu began thinking about opportunities to streamline the process.</p> <p>“In some cases, the bottlenecks in genetic medicine aren’t the science anymore,” he said. “They’re in meeting regulatory requirements, in the manufacturing costs associated with these treatments, and in the commercial challenges of drugs that treat very small numbers of patients. Witnessing gene-editing companies make the gut-wrenching decisions of which targets to pursue — synonymous with the gut-wrenching decisions of which patients are left behind — made it clear that we need creative scientific ways to help address some of these problems.”</p> <p>The team found a potential solution by identifying a common cause of many different genetic diseases. Normally, when a cell needs to make a protein, it first transcribes DNA into mRNA. Other molecules called tRNAs then read the mRNA sequence and bring the corresponding amino acid building blocks together into a chain that becomes the final protein. A special three-letter sequence in the mRNA — UAA, UAG, or UGA — marks the end of the protein assembly instructions. This signal is called a termination codon.</p> <p>But roughly 30 percent of genetic diseases are caused by DNA mutations that create an errant termination codon somewhere in the middle of the mRNA sequence, signaling the cell to halt protein production too early. Liu’s team sought to develop a universal way to permanently equip the cell to overcome these premature termination codons, allowing protein synthesis to continue as normal.</p> <p>“Our hope is that this type of solution could provide a single, one-time gene-editing treatment that benefits patients with different diseases caused by nonsense mutations,” said Pierce.</p> <h2>Installing a new tRNA</h2> <p>The researchers came up with a creative application of prime editing to tackle this issue. They first turned to “suppressor” tRNAs. This type of tRNA adds an amino acid building block in response to a premature termination codon, allowing the cell to continue building the protein instead of halting protein synthesis midway. </p> <p>By testing tens of thousands of tRNA variants, Pierce, Erwood, and their colleagues engineered a new, highly efficient suppressor tRNA. They then optimized a prime editing system to install this tRNA directly into the genomes of cells, replacing an existing, redundant tRNA. </p> <p>“A lot of what made this possible was simply taking advantage of how versatile prime editing is,” said Erwood. “It let us make very complex changes to a tRNA in ways we couldn’t have done otherwise. We tested thousands of different prime edits until one tRNA design finally stood out.”</p> <p>The resulting prime editor permanently equips cells with the new suppressor tRNA, which allows them to produce full-length protein regardless of which specific gene is carrying a nonsense mutation.</p> <p>The researchers used prime editing to install this new suppressor tRNA in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1. Using the same prime editing system in these different cell models, they observed enzyme activity restored at approximately 20 to 70 percent of normal levels, a level theoretically high enough to alleviate disease symptoms.</p> <p>The team also tested their strategy in a mouse model of Hurler syndrome, a lysosomal storage disorder. When the scientists analyzed tissue from the mouse brain, liver, and spleen — tissues normally impacted by the disorder — they determined that PERT had restored about 6 percent of normal enzyme activity, high enough to nearly eliminate all signs of disease.</p> <p>The researchers found that PERT did not result in detected off-target edits, and did not affect the normal synthesis of other proteins. The team speculates that PERT minimally impacts normal protein production because mammalian cells have several additional ways of supporting proper protein synthesis, and because PERT leads to only low levels of the engineered suppressor tRNA in cells.</p> <p>The team is now further optimizing PERT and testing it in a variety of animal models for different genetic diseases.</p> <p>“We hope this research will eventually pave the way for a clinical trial of PERT, and will inspire other broadly applicable, disease-agnostic gene-editing strategies,” said Liu. “If you don’t have to target one mutation at a time, the size of the patient groups that could be treated with a single drug becomes much, much larger. We hope the result will be many more patients that benefit, as well as greater incentives to develop gene-editing drugs for rare diseases.”</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>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Pierce SE, Erwood S, et al. <a href="https://www.nature.com/articles/s41586-025-09732-2" target="_blank">Prime editing-installed suppressor tRNAs for disease-agnostic genome editing</a>. <em>Nature</em>. Online November 19, 2025. DOI: 10.1038/s41586-025-09732-2.</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>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This study was funded by the National Institutes of Health, the ӳ����ý Chemical Biology and Therapeutics Science program funds, and Howard Hughes Medical Institute.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/gene-therapy" hreflang="en">Gene therapy</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Wed, 10 Jul 2024 09:00:00 +0000 adicorat 5557111 at /news/therapy-candidate-fatal-prion-diseases-turns-disease-causing-gene <span class="field field--name-title field--type-string field--label-hidden"><h1>Single prime editing system could potentially treat multiple genetic diseases</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Karen Zusi-Tran</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-11-19T12:01:34-05:00" class="datetime">November 19, 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>Single prime editing system could potentially treat multiple genetic diseases</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>Researchers have developed a genome-editing strategy that targets a common cause of roughly 30 percent of rare diseases and could vastly improve access to gene-editing treatments for patients.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Karen Zusi-Tran </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="2025-11-19T12:01:34-05:00" title="Wednesday, November 19, 2025 - 12:01" class="datetime">November 19, 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 role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DSs035QC 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=UTVl6XHv 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=2GnfN8NZ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Agnieszka Grosso, ӳ����ý Communications </div> <div class="media-caption__description"> A single prime editing system could potentially treat multiple genetic diseases. </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/2411/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2411/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2411/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="font-family:Open Sans;background-color:#f3f3f3;padding:2em;margin-bottom:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">The new prime editing strategy addresses “nonsense mutations,” a class of mutations that halt protein production too early and can cause about one-third of genetic diseases. </li> <li aria-level="1">David Liu and his team showed that their strategy restores protein production and function in cell and animal models of four different rare diseases.</li> <li aria-level="1">This approach could streamline the development of gene-editing medicines that benefit many patients with nonsense mutations, regardless of their specific disease.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells" target="_blank">New CRISPR genome editing system offers a wide range of versatility in human cells</a></div> <div class="field__item"><a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" target="_blank">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</a></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>A team of researchers at the ӳ����ý, led by gene-editing pioneer <a href="/bios/david-liu">David Liu</a>, has developed a new genome-editing strategy that could potentially lead to a one-time treatment for multiple unrelated genetic diseases.</p> <p>Gene-editing medicines are often made one at a time to treat a specific mutation, an approach that’s difficult to scale up to address the thousands of rare diseases affecting patients around the world. The new technology, called PERT (prime editing-mediated readthrough of premature termination codons), is designed to maximize the potential of gene editing by using just one editing agent to serve as many patients as possible.</p> <p>“We're excited by the possibility that you could develop a single editing agent into a drug that may help many different types of patients, circumventing the need to invest multiple years and millions of dollars to develop each new genetic medicine for each individual,” said Liu, a core institute member, the Richard Merkin Professor, and director of the Merkin Institute for Transformative Technologies in Healthcare at ӳ����ý, the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>PERT uses prime editing — a versatile and precise DNA editing system <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">developed by Liu’s lab</a> in 2019 — to rescue a type of mutation that can cause about a third of rare diseases. These “nonsense mutations” can appear in many different genes and cause cells to stop synthesizing their associated proteins too early, resulting in truncated, malfunctioning molecules that lead to disease. Among the 200,000 disease-causing mutations documented in the ClinVar database, 24 percent are nonsense mutations.</p> <p>The PERT approach does not directly edit these nonsense mutations — a strategy that would require developing a different editing agent for each mutation — but instead makes another edit that equips cells with a tool to produce the normal, functional version of the protein, regardless of which gene is impacted.</p> <p>In a paper published in <a href="https://www.nature.com/articles/s41586-025-09732-2"><em>Nature</em></a>, the team described how they tested PERT in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1, and in a mouse model of Hurler syndrome. The technology restored protein production and alleviated disease symptoms, with no detected off-target edits, changes in normal RNA or protein production, or toxicity to the cells.</p> <p>The work was spearheaded by co-first authors Sarah Pierce and Steven Erwood, both postdoctoral associates in the Liu lab.</p> <h2>A creative solution</h2> <p>Liu and his lab have been developing new DNA-editing tools to address genetic diseases for many years. However, after seeing how challenging and resource-intensive it is for these technologies to reach patients, Liu began thinking about opportunities to streamline the process.</p> <p>“In some cases, the bottlenecks in genetic medicine aren’t the science anymore,” he said. “They’re in meeting regulatory requirements, in the manufacturing costs associated with these treatments, and in the commercial challenges of drugs that treat very small numbers of patients. Witnessing gene-editing companies make the gut-wrenching decisions of which targets to pursue — synonymous with the gut-wrenching decisions of which patients are left behind — made it clear that we need creative scientific ways to help address some of these problems.”</p> <p>The team found a potential solution by identifying a common cause of many different genetic diseases. Normally, when a cell needs to make a protein, it first transcribes DNA into mRNA. Other molecules called tRNAs then read the mRNA sequence and bring the corresponding amino acid building blocks together into a chain that becomes the final protein. A special three-letter sequence in the mRNA — UAA, UAG, or UGA — marks the end of the protein assembly instructions. This signal is called a termination codon.</p> <p>But roughly 30 percent of genetic diseases are caused by DNA mutations that create an errant termination codon somewhere in the middle of the mRNA sequence, signaling the cell to halt protein production too early. Liu’s team sought to develop a universal way to permanently equip the cell to overcome these premature termination codons, allowing protein synthesis to continue as normal.</p> <p>“Our hope is that this type of solution could provide a single, one-time gene-editing treatment that benefits patients with different diseases caused by nonsense mutations,” said Pierce.</p> <h2>Installing a new tRNA</h2> <p>The researchers came up with a creative application of prime editing to tackle this issue. They first turned to “suppressor” tRNAs. This type of tRNA adds an amino acid building block in response to a premature termination codon, allowing the cell to continue building the protein instead of halting protein synthesis midway. </p> <p>By testing tens of thousands of tRNA variants, Pierce, Erwood, and their colleagues engineered a new, highly efficient suppressor tRNA. They then optimized a prime editing system to install this tRNA directly into the genomes of cells, replacing an existing, redundant tRNA. </p> <p>“A lot of what made this possible was simply taking advantage of how versatile prime editing is,” said Erwood. “It let us make very complex changes to a tRNA in ways we couldn’t have done otherwise. We tested thousands of different prime edits until one tRNA design finally stood out.”</p> <p>The resulting prime editor permanently equips cells with the new suppressor tRNA, which allows them to produce full-length protein regardless of which specific gene is carrying a nonsense mutation.</p> <p>The researchers used prime editing to install this new suppressor tRNA in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1. Using the same prime editing system in these different cell models, they observed enzyme activity restored at approximately 20 to 70 percent of normal levels, a level theoretically high enough to alleviate disease symptoms.</p> <p>The team also tested their strategy in a mouse model of Hurler syndrome, a lysosomal storage disorder. When the scientists analyzed tissue from the mouse brain, liver, and spleen — tissues normally impacted by the disorder — they determined that PERT had restored about 6 percent of normal enzyme activity, high enough to nearly eliminate all signs of disease.</p> <p>The researchers found that PERT did not result in detected off-target edits, and did not affect the normal synthesis of other proteins. The team speculates that PERT minimally impacts normal protein production because mammalian cells have several additional ways of supporting proper protein synthesis, and because PERT leads to only low levels of the engineered suppressor tRNA in cells.</p> <p>The team is now further optimizing PERT and testing it in a variety of animal models for different genetic diseases.</p> <p>“We hope this research will eventually pave the way for a clinical trial of PERT, and will inspire other broadly applicable, disease-agnostic gene-editing strategies,” said Liu. “If you don’t have to target one mutation at a time, the size of the patient groups that could be treated with a single drug becomes much, much larger. We hope the result will be many more patients that benefit, as well as greater incentives to develop gene-editing drugs for rare diseases.”</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>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Pierce SE, Erwood S, et al. <a href="https://www.nature.com/articles/s41586-025-09732-2" target="_blank">Prime editing-installed suppressor tRNAs for disease-agnostic genome editing</a>. <em>Nature</em>. Online November 19, 2025. DOI: 10.1038/s41586-025-09732-2.</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>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This study was funded by the National Institutes of Health, the ӳ����ý Chemical Biology and Therapeutics Science program funds, and Howard Hughes Medical Institute.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/gene-therapy" hreflang="en">Gene therapy</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Thu, 27 Jun 2024 18:11:10 +0000 Corie Lok 5557021 at /news/improved-prime-editing-system-makes-gene-sized-edits-human-cells-therapeutic-levels <span class="field field--name-title field--type-string field--label-hidden"><h1>Single prime editing system could potentially treat multiple genetic diseases</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Karen Zusi-Tran</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-11-19T12:01:34-05:00" class="datetime">November 19, 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>Single prime editing system could potentially treat multiple genetic diseases</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>Researchers have developed a genome-editing strategy that targets a common cause of roughly 30 percent of rare diseases and could vastly improve access to gene-editing treatments for patients.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Karen Zusi-Tran </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="2025-11-19T12:01:34-05:00" title="Wednesday, November 19, 2025 - 12:01" class="datetime">November 19, 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 role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DSs035QC 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=UTVl6XHv 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=2GnfN8NZ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Agnieszka Grosso, ӳ����ý Communications </div> <div class="media-caption__description"> A single prime editing system could potentially treat multiple genetic diseases. </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/2411/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2411/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2411/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="font-family:Open Sans;background-color:#f3f3f3;padding:2em;margin-bottom:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">The new prime editing strategy addresses “nonsense mutations,” a class of mutations that halt protein production too early and can cause about one-third of genetic diseases. </li> <li aria-level="1">David Liu and his team showed that their strategy restores protein production and function in cell and animal models of four different rare diseases.</li> <li aria-level="1">This approach could streamline the development of gene-editing medicines that benefit many patients with nonsense mutations, regardless of their specific disease.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells" target="_blank">New CRISPR genome editing system offers a wide range of versatility in human cells</a></div> <div class="field__item"><a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" target="_blank">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</a></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>A team of researchers at the ӳ����ý, led by gene-editing pioneer <a href="/bios/david-liu">David Liu</a>, has developed a new genome-editing strategy that could potentially lead to a one-time treatment for multiple unrelated genetic diseases.</p> <p>Gene-editing medicines are often made one at a time to treat a specific mutation, an approach that’s difficult to scale up to address the thousands of rare diseases affecting patients around the world. The new technology, called PERT (prime editing-mediated readthrough of premature termination codons), is designed to maximize the potential of gene editing by using just one editing agent to serve as many patients as possible.</p> <p>“We're excited by the possibility that you could develop a single editing agent into a drug that may help many different types of patients, circumventing the need to invest multiple years and millions of dollars to develop each new genetic medicine for each individual,” said Liu, a core institute member, the Richard Merkin Professor, and director of the Merkin Institute for Transformative Technologies in Healthcare at ӳ����ý, the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>PERT uses prime editing — a versatile and precise DNA editing system <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">developed by Liu’s lab</a> in 2019 — to rescue a type of mutation that can cause about a third of rare diseases. These “nonsense mutations” can appear in many different genes and cause cells to stop synthesizing their associated proteins too early, resulting in truncated, malfunctioning molecules that lead to disease. Among the 200,000 disease-causing mutations documented in the ClinVar database, 24 percent are nonsense mutations.</p> <p>The PERT approach does not directly edit these nonsense mutations — a strategy that would require developing a different editing agent for each mutation — but instead makes another edit that equips cells with a tool to produce the normal, functional version of the protein, regardless of which gene is impacted.</p> <p>In a paper published in <a href="https://www.nature.com/articles/s41586-025-09732-2"><em>Nature</em></a>, the team described how they tested PERT in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1, and in a mouse model of Hurler syndrome. The technology restored protein production and alleviated disease symptoms, with no detected off-target edits, changes in normal RNA or protein production, or toxicity to the cells.</p> <p>The work was spearheaded by co-first authors Sarah Pierce and Steven Erwood, both postdoctoral associates in the Liu lab.</p> <h2>A creative solution</h2> <p>Liu and his lab have been developing new DNA-editing tools to address genetic diseases for many years. However, after seeing how challenging and resource-intensive it is for these technologies to reach patients, Liu began thinking about opportunities to streamline the process.</p> <p>“In some cases, the bottlenecks in genetic medicine aren’t the science anymore,” he said. “They’re in meeting regulatory requirements, in the manufacturing costs associated with these treatments, and in the commercial challenges of drugs that treat very small numbers of patients. Witnessing gene-editing companies make the gut-wrenching decisions of which targets to pursue — synonymous with the gut-wrenching decisions of which patients are left behind — made it clear that we need creative scientific ways to help address some of these problems.”</p> <p>The team found a potential solution by identifying a common cause of many different genetic diseases. Normally, when a cell needs to make a protein, it first transcribes DNA into mRNA. Other molecules called tRNAs then read the mRNA sequence and bring the corresponding amino acid building blocks together into a chain that becomes the final protein. A special three-letter sequence in the mRNA — UAA, UAG, or UGA — marks the end of the protein assembly instructions. This signal is called a termination codon.</p> <p>But roughly 30 percent of genetic diseases are caused by DNA mutations that create an errant termination codon somewhere in the middle of the mRNA sequence, signaling the cell to halt protein production too early. Liu’s team sought to develop a universal way to permanently equip the cell to overcome these premature termination codons, allowing protein synthesis to continue as normal.</p> <p>“Our hope is that this type of solution could provide a single, one-time gene-editing treatment that benefits patients with different diseases caused by nonsense mutations,” said Pierce.</p> <h2>Installing a new tRNA</h2> <p>The researchers came up with a creative application of prime editing to tackle this issue. They first turned to “suppressor” tRNAs. This type of tRNA adds an amino acid building block in response to a premature termination codon, allowing the cell to continue building the protein instead of halting protein synthesis midway. </p> <p>By testing tens of thousands of tRNA variants, Pierce, Erwood, and their colleagues engineered a new, highly efficient suppressor tRNA. They then optimized a prime editing system to install this tRNA directly into the genomes of cells, replacing an existing, redundant tRNA. </p> <p>“A lot of what made this possible was simply taking advantage of how versatile prime editing is,” said Erwood. “It let us make very complex changes to a tRNA in ways we couldn’t have done otherwise. We tested thousands of different prime edits until one tRNA design finally stood out.”</p> <p>The resulting prime editor permanently equips cells with the new suppressor tRNA, which allows them to produce full-length protein regardless of which specific gene is carrying a nonsense mutation.</p> <p>The researchers used prime editing to install this new suppressor tRNA in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1. Using the same prime editing system in these different cell models, they observed enzyme activity restored at approximately 20 to 70 percent of normal levels, a level theoretically high enough to alleviate disease symptoms.</p> <p>The team also tested their strategy in a mouse model of Hurler syndrome, a lysosomal storage disorder. When the scientists analyzed tissue from the mouse brain, liver, and spleen — tissues normally impacted by the disorder — they determined that PERT had restored about 6 percent of normal enzyme activity, high enough to nearly eliminate all signs of disease.</p> <p>The researchers found that PERT did not result in detected off-target edits, and did not affect the normal synthesis of other proteins. The team speculates that PERT minimally impacts normal protein production because mammalian cells have several additional ways of supporting proper protein synthesis, and because PERT leads to only low levels of the engineered suppressor tRNA in cells.</p> <p>The team is now further optimizing PERT and testing it in a variety of animal models for different genetic diseases.</p> <p>“We hope this research will eventually pave the way for a clinical trial of PERT, and will inspire other broadly applicable, disease-agnostic gene-editing strategies,” said Liu. “If you don’t have to target one mutation at a time, the size of the patient groups that could be treated with a single drug becomes much, much larger. We hope the result will be many more patients that benefit, as well as greater incentives to develop gene-editing drugs for rare diseases.”</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>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Pierce SE, Erwood S, et al. <a href="https://www.nature.com/articles/s41586-025-09732-2" target="_blank">Prime editing-installed suppressor tRNAs for disease-agnostic genome editing</a>. <em>Nature</em>. Online November 19, 2025. DOI: 10.1038/s41586-025-09732-2.</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>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This study was funded by the National Institutes of Health, the ӳ����ý Chemical Biology and Therapeutics Science program funds, and Howard Hughes Medical Institute.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/gene-therapy" hreflang="en">Gene therapy</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Mon, 10 Jun 2024 09:30:00 +0000 adicorat 5556946 at /news/prime-editing-shows-proof-concept-treating-sickle-cell-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Single prime editing system could potentially treat multiple genetic diseases</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Karen Zusi-Tran</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-11-19T12:01:34-05:00" class="datetime">November 19, 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>Single prime editing system could potentially treat multiple genetic diseases</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>Researchers have developed a genome-editing strategy that targets a common cause of roughly 30 percent of rare diseases and could vastly improve access to gene-editing treatments for patients.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Karen Zusi-Tran </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="2025-11-19T12:01:34-05:00" title="Wednesday, November 19, 2025 - 12:01" class="datetime">November 19, 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 role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DSs035QC 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=UTVl6XHv 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=2GnfN8NZ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Agnieszka Grosso, ӳ����ý Communications </div> <div class="media-caption__description"> A single prime editing system could potentially treat multiple genetic diseases. </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/2411/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2411/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2411/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="font-family:Open Sans;background-color:#f3f3f3;padding:2em;margin-bottom:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">The new prime editing strategy addresses “nonsense mutations,” a class of mutations that halt protein production too early and can cause about one-third of genetic diseases. </li> <li aria-level="1">David Liu and his team showed that their strategy restores protein production and function in cell and animal models of four different rare diseases.</li> <li aria-level="1">This approach could streamline the development of gene-editing medicines that benefit many patients with nonsense mutations, regardless of their specific disease.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells" target="_blank">New CRISPR genome editing system offers a wide range of versatility in human cells</a></div> <div class="field__item"><a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" target="_blank">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</a></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>A team of researchers at the ӳ����ý, led by gene-editing pioneer <a href="/bios/david-liu">David Liu</a>, has developed a new genome-editing strategy that could potentially lead to a one-time treatment for multiple unrelated genetic diseases.</p> <p>Gene-editing medicines are often made one at a time to treat a specific mutation, an approach that’s difficult to scale up to address the thousands of rare diseases affecting patients around the world. The new technology, called PERT (prime editing-mediated readthrough of premature termination codons), is designed to maximize the potential of gene editing by using just one editing agent to serve as many patients as possible.</p> <p>“We're excited by the possibility that you could develop a single editing agent into a drug that may help many different types of patients, circumventing the need to invest multiple years and millions of dollars to develop each new genetic medicine for each individual,” said Liu, a core institute member, the Richard Merkin Professor, and director of the Merkin Institute for Transformative Technologies in Healthcare at ӳ����ý, the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>PERT uses prime editing — a versatile and precise DNA editing system <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">developed by Liu’s lab</a> in 2019 — to rescue a type of mutation that can cause about a third of rare diseases. These “nonsense mutations” can appear in many different genes and cause cells to stop synthesizing their associated proteins too early, resulting in truncated, malfunctioning molecules that lead to disease. Among the 200,000 disease-causing mutations documented in the ClinVar database, 24 percent are nonsense mutations.</p> <p>The PERT approach does not directly edit these nonsense mutations — a strategy that would require developing a different editing agent for each mutation — but instead makes another edit that equips cells with a tool to produce the normal, functional version of the protein, regardless of which gene is impacted.</p> <p>In a paper published in <a href="https://www.nature.com/articles/s41586-025-09732-2"><em>Nature</em></a>, the team described how they tested PERT in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1, and in a mouse model of Hurler syndrome. The technology restored protein production and alleviated disease symptoms, with no detected off-target edits, changes in normal RNA or protein production, or toxicity to the cells.</p> <p>The work was spearheaded by co-first authors Sarah Pierce and Steven Erwood, both postdoctoral associates in the Liu lab.</p> <h2>A creative solution</h2> <p>Liu and his lab have been developing new DNA-editing tools to address genetic diseases for many years. However, after seeing how challenging and resource-intensive it is for these technologies to reach patients, Liu began thinking about opportunities to streamline the process.</p> <p>“In some cases, the bottlenecks in genetic medicine aren’t the science anymore,” he said. “They’re in meeting regulatory requirements, in the manufacturing costs associated with these treatments, and in the commercial challenges of drugs that treat very small numbers of patients. Witnessing gene-editing companies make the gut-wrenching decisions of which targets to pursue — synonymous with the gut-wrenching decisions of which patients are left behind — made it clear that we need creative scientific ways to help address some of these problems.”</p> <p>The team found a potential solution by identifying a common cause of many different genetic diseases. Normally, when a cell needs to make a protein, it first transcribes DNA into mRNA. Other molecules called tRNAs then read the mRNA sequence and bring the corresponding amino acid building blocks together into a chain that becomes the final protein. A special three-letter sequence in the mRNA — UAA, UAG, or UGA — marks the end of the protein assembly instructions. This signal is called a termination codon.</p> <p>But roughly 30 percent of genetic diseases are caused by DNA mutations that create an errant termination codon somewhere in the middle of the mRNA sequence, signaling the cell to halt protein production too early. Liu’s team sought to develop a universal way to permanently equip the cell to overcome these premature termination codons, allowing protein synthesis to continue as normal.</p> <p>“Our hope is that this type of solution could provide a single, one-time gene-editing treatment that benefits patients with different diseases caused by nonsense mutations,” said Pierce.</p> <h2>Installing a new tRNA</h2> <p>The researchers came up with a creative application of prime editing to tackle this issue. They first turned to “suppressor” tRNAs. This type of tRNA adds an amino acid building block in response to a premature termination codon, allowing the cell to continue building the protein instead of halting protein synthesis midway. </p> <p>By testing tens of thousands of tRNA variants, Pierce, Erwood, and their colleagues engineered a new, highly efficient suppressor tRNA. They then optimized a prime editing system to install this tRNA directly into the genomes of cells, replacing an existing, redundant tRNA. </p> <p>“A lot of what made this possible was simply taking advantage of how versatile prime editing is,” said Erwood. “It let us make very complex changes to a tRNA in ways we couldn’t have done otherwise. We tested thousands of different prime edits until one tRNA design finally stood out.”</p> <p>The resulting prime editor permanently equips cells with the new suppressor tRNA, which allows them to produce full-length protein regardless of which specific gene is carrying a nonsense mutation.</p> <p>The researchers used prime editing to install this new suppressor tRNA in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1. Using the same prime editing system in these different cell models, they observed enzyme activity restored at approximately 20 to 70 percent of normal levels, a level theoretically high enough to alleviate disease symptoms.</p> <p>The team also tested their strategy in a mouse model of Hurler syndrome, a lysosomal storage disorder. When the scientists analyzed tissue from the mouse brain, liver, and spleen — tissues normally impacted by the disorder — they determined that PERT had restored about 6 percent of normal enzyme activity, high enough to nearly eliminate all signs of disease.</p> <p>The researchers found that PERT did not result in detected off-target edits, and did not affect the normal synthesis of other proteins. The team speculates that PERT minimally impacts normal protein production because mammalian cells have several additional ways of supporting proper protein synthesis, and because PERT leads to only low levels of the engineered suppressor tRNA in cells.</p> <p>The team is now further optimizing PERT and testing it in a variety of animal models for different genetic diseases.</p> <p>“We hope this research will eventually pave the way for a clinical trial of PERT, and will inspire other broadly applicable, disease-agnostic gene-editing strategies,” said Liu. “If you don’t have to target one mutation at a time, the size of the patient groups that could be treated with a single drug becomes much, much larger. We hope the result will be many more patients that benefit, as well as greater incentives to develop gene-editing drugs for rare diseases.”</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>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Pierce SE, Erwood S, et al. <a href="https://www.nature.com/articles/s41586-025-09732-2" target="_blank">Prime editing-installed suppressor tRNAs for disease-agnostic genome editing</a>. <em>Nature</em>. Online November 19, 2025. DOI: 10.1038/s41586-025-09732-2.</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>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This study was funded by the National Institutes of Health, the ӳ����ý Chemical Biology and Therapeutics Science program funds, and Howard Hughes Medical Institute.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/gene-therapy" hreflang="en">Gene therapy</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Mon, 17 Apr 2023 15:53:54 +0000 kzusi@broadinstitute.org 1282061 at /news/base-editing-treats-spinal-muscular-atrophy-mice <span class="field field--name-title field--type-string field--label-hidden"><h1>Single prime editing system could potentially treat multiple genetic diseases</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Karen Zusi-Tran</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-11-19T12:01:34-05:00" class="datetime">November 19, 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>Single prime editing system could potentially treat multiple genetic diseases</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>Researchers have developed a genome-editing strategy that targets a common cause of roughly 30 percent of rare diseases and could vastly improve access to gene-editing treatments for patients.</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Karen Zusi-Tran </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="2025-11-19T12:01:34-05:00" title="Wednesday, November 19, 2025 - 12:01" class="datetime">November 19, 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 role="img" aria-label="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients."> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1921px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=pMp9OkNK 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/png" width="754" height="503"/> <source srcset="/files/styles/multiple_ct_header_desktop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DSs035QC 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/png" width="736" height="520"/> <source srcset="/files/styles/multiple_ct_header_laptop/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=UTVl6XHv 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/png" width="641" height="451"/> <source srcset="/files/styles/multiple_ct_header_tablet/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=2GnfN8NZ 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/png" width="706" height="417"/> <source srcset="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP 1x" media="all and (max-width: 539px)" type="image/png" width="499" height="294"/> <img loading="eager" width="499" height="294" src="/files/styles/multiple_ct_header_phone/public/longstory/Gene%20Editing_David%20Liu_Main%20News%20Story%20image_v4_Option%202.png?h=a7d067a7&itok=DfzAiHEP" alt="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." title="A graphic displaying an oval containing a DNA double helix with several base pairs highlighted, connected to four icons representing patients." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Agnieszka Grosso, ӳ����ý Communications </div> <div class="media-caption__description"> A single prime editing system could potentially treat multiple genetic diseases. </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/2411/feed&title=" target="_blank" title="Share to Facebook" aria-label="Share to Facebook" class="social-sharing-buttons-button share-facebook" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#facebook" /> </svg> </a> <a href="https://twitter.com/intent/tweet?text=+/taxonomy/term/2411/feed" target="_blank" title="Share to X" aria-label="Share to X" class="social-sharing-buttons-button share-x" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#x" /> </svg> </a> <a href="mailto:?subject=&body=/taxonomy/term/2411/feed" title="Share to Email" aria-label="Share to Email" class="social-sharing-buttons-button share-email" target="_blank" rel="noopener"> <svg aria-hidden="true" width="32px" height="32px" style="border-radius:100%;"> <use href="/modules/contrib/better_social_sharing_buttons/assets/dist/sprites/social-icons--no-color.svg#email" /> </svg> </a> </div> </div> <div class="block block-layout-builder block-field-blocknodelong-storyfield-content-paragraphs"> <div class="field field--name-field-content-paragraphs field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-narrow paragraph--view-mode--default"> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><div class="clearfix" style="font-family:Open Sans;background-color:#f3f3f3;padding:2em;margin-bottom:2em;"> <h3>Highlights</h3> <ul> <li aria-level="1">The new prime editing strategy addresses “nonsense mutations,” a class of mutations that halt protein production too early and can cause about one-third of genetic diseases. </li> <li aria-level="1">David Liu and his team showed that their strategy restores protein production and function in cell and animal models of four different rare diseases.</li> <li aria-level="1">This approach could streamline the development of gene-editing medicines that benefit many patients with nonsense mutations, regardless of their specific disease.</li> </ul> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells" target="_blank">New CRISPR genome editing system offers a wide range of versatility in human cells</a></div> <div class="field__item"><a href="/news/qa-one-scientists-bold-vision-make-demand-treatments-routine-life-threatening-rare-genetic" target="_blank">Q&A: David Liu’s bold vision to make on-demand treatments routine for life-threatening rare genetic diseases</a></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>A team of researchers at the ӳ����ý, led by gene-editing pioneer <a href="/bios/david-liu">David Liu</a>, has developed a new genome-editing strategy that could potentially lead to a one-time treatment for multiple unrelated genetic diseases.</p> <p>Gene-editing medicines are often made one at a time to treat a specific mutation, an approach that’s difficult to scale up to address the thousands of rare diseases affecting patients around the world. The new technology, called PERT (prime editing-mediated readthrough of premature termination codons), is designed to maximize the potential of gene editing by using just one editing agent to serve as many patients as possible.</p> <p>“We're excited by the possibility that you could develop a single editing agent into a drug that may help many different types of patients, circumventing the need to invest multiple years and millions of dollars to develop each new genetic medicine for each individual,” said Liu, a core institute member, the Richard Merkin Professor, and director of the Merkin Institute for Transformative Technologies in Healthcare at ӳ����ý, the Dudley Cabot Professor of the Natural Sciences in the Faculty of Arts and Sciences at Harvard University, and Howard Hughes Medical Institute investigator.</p> <p>PERT uses prime editing — a versatile and precise DNA editing system <a href="/news/new-crispr-genome-editing-system-offers-wide-range-versatility-human-cells">developed by Liu’s lab</a> in 2019 — to rescue a type of mutation that can cause about a third of rare diseases. These “nonsense mutations” can appear in many different genes and cause cells to stop synthesizing their associated proteins too early, resulting in truncated, malfunctioning molecules that lead to disease. Among the 200,000 disease-causing mutations documented in the ClinVar database, 24 percent are nonsense mutations.</p> <p>The PERT approach does not directly edit these nonsense mutations — a strategy that would require developing a different editing agent for each mutation — but instead makes another edit that equips cells with a tool to produce the normal, functional version of the protein, regardless of which gene is impacted.</p> <p>In a paper published in <a href="https://www.nature.com/articles/s41586-025-09732-2"><em>Nature</em></a>, the team described how they tested PERT in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1, and in a mouse model of Hurler syndrome. The technology restored protein production and alleviated disease symptoms, with no detected off-target edits, changes in normal RNA or protein production, or toxicity to the cells.</p> <p>The work was spearheaded by co-first authors Sarah Pierce and Steven Erwood, both postdoctoral associates in the Liu lab.</p> <h2>A creative solution</h2> <p>Liu and his lab have been developing new DNA-editing tools to address genetic diseases for many years. However, after seeing how challenging and resource-intensive it is for these technologies to reach patients, Liu began thinking about opportunities to streamline the process.</p> <p>“In some cases, the bottlenecks in genetic medicine aren’t the science anymore,” he said. “They’re in meeting regulatory requirements, in the manufacturing costs associated with these treatments, and in the commercial challenges of drugs that treat very small numbers of patients. Witnessing gene-editing companies make the gut-wrenching decisions of which targets to pursue — synonymous with the gut-wrenching decisions of which patients are left behind — made it clear that we need creative scientific ways to help address some of these problems.”</p> <p>The team found a potential solution by identifying a common cause of many different genetic diseases. Normally, when a cell needs to make a protein, it first transcribes DNA into mRNA. Other molecules called tRNAs then read the mRNA sequence and bring the corresponding amino acid building blocks together into a chain that becomes the final protein. A special three-letter sequence in the mRNA — UAA, UAG, or UGA — marks the end of the protein assembly instructions. This signal is called a termination codon.</p> <p>But roughly 30 percent of genetic diseases are caused by DNA mutations that create an errant termination codon somewhere in the middle of the mRNA sequence, signaling the cell to halt protein production too early. Liu’s team sought to develop a universal way to permanently equip the cell to overcome these premature termination codons, allowing protein synthesis to continue as normal.</p> <p>“Our hope is that this type of solution could provide a single, one-time gene-editing treatment that benefits patients with different diseases caused by nonsense mutations,” said Pierce.</p> <h2>Installing a new tRNA</h2> <p>The researchers came up with a creative application of prime editing to tackle this issue. They first turned to “suppressor” tRNAs. This type of tRNA adds an amino acid building block in response to a premature termination codon, allowing the cell to continue building the protein instead of halting protein synthesis midway. </p> <p>By testing tens of thousands of tRNA variants, Pierce, Erwood, and their colleagues engineered a new, highly efficient suppressor tRNA. They then optimized a prime editing system to install this tRNA directly into the genomes of cells, replacing an existing, redundant tRNA. </p> <p>“A lot of what made this possible was simply taking advantage of how versatile prime editing is,” said Erwood. “It let us make very complex changes to a tRNA in ways we couldn’t have done otherwise. We tested thousands of different prime edits until one tRNA design finally stood out.”</p> <p>The resulting prime editor permanently equips cells with the new suppressor tRNA, which allows them to produce full-length protein regardless of which specific gene is carrying a nonsense mutation.</p> <p>The researchers used prime editing to install this new suppressor tRNA in human cell models of Batten disease, Tay-Sachs disease, and Niemann-Pick disease type C1. Using the same prime editing system in these different cell models, they observed enzyme activity restored at approximately 20 to 70 percent of normal levels, a level theoretically high enough to alleviate disease symptoms.</p> <p>The team also tested their strategy in a mouse model of Hurler syndrome, a lysosomal storage disorder. When the scientists analyzed tissue from the mouse brain, liver, and spleen — tissues normally impacted by the disorder — they determined that PERT had restored about 6 percent of normal enzyme activity, high enough to nearly eliminate all signs of disease.</p> <p>The researchers found that PERT did not result in detected off-target edits, and did not affect the normal synthesis of other proteins. The team speculates that PERT minimally impacts normal protein production because mammalian cells have several additional ways of supporting proper protein synthesis, and because PERT leads to only low levels of the engineered suppressor tRNA in cells.</p> <p>The team is now further optimizing PERT and testing it in a variety of animal models for different genetic diseases.</p> <p>“We hope this research will eventually pave the way for a clinical trial of PERT, and will inspire other broadly applicable, disease-agnostic gene-editing strategies,” said Liu. “If you don’t have to target one mutation at a time, the size of the patient groups that could be treated with a single drug becomes much, much larger. We hope the result will be many more patients that benefit, as well as greater incentives to develop gene-editing drugs for rare diseases.”</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>Paper cited</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>Pierce SE, Erwood S, et al. <a href="https://www.nature.com/articles/s41586-025-09732-2" target="_blank">Prime editing-installed suppressor tRNAs for disease-agnostic genome editing</a>. <em>Nature</em>. Online November 19, 2025. DOI: 10.1038/s41586-025-09732-2.</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>Funding</p> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>This study was funded by the National Institutes of Health, the ӳ����ý Chemical Biology and Therapeutics Science program funds, and Howard Hughes Medical Institute.</p> </div> </div> </div> </div> </div> </div> </div> </div> </div> </div> <div class="content-section container"> <div class="content-section__main"> <div class="block-node-broad-tags block block-layout-builder block-field-blocknodelong-storyfield-broad-tags"> <div class="block-node-broad-tags__row"> <div class="block-node-broad-tags__title">Tags:</div> <div class="field field--name-field-broad-tags field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><a href="/broad-tags/liu-lab" hreflang="en">Liu Lab</a></div> <div class="field__item"><a href="/broad-tags/merkin-institute-transformative-technologies-healthcare" hreflang="en">Merkin Institute for Transformative Technologies in Healthcare</a></div> <div class="field__item"><a href="/broad-tags/rare-disease" hreflang="en">Rare Disease</a></div> <div class="field__item"><a href="/broad-tags/gene-therapy" hreflang="en">Gene therapy</a></div> <div class="field__item"><a href="/broad-tags/david-liu" hreflang="en">David Liu</a></div> </div> </div> </div> </div> </div> Thu, 30 Mar 2023 18:00:24 +0000 adicorat 1281896 at