/ en Wed, 06 Aug 25 15:06:44 -0400 /news/technology-brings-new-precision-to-genome-editing <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists develop technology that brings new precision to genome editing</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-06T15:06:44-04:00" class="datetime">August 6, 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>Scientists develop technology that brings new precision to genome editing</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>Fast-acting, cell-permeable protein system that controls CRISPR-Cas9 could reduce off-target effects and advance gene therapy</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Danielle Doughty, MIT Department of Chemistry </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="2025-08-06T15:06:44-04:00" title="Wednesday, August 6, 2025 - 15:06" class="datetime">August 6, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=IvFcJmC1 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=64ear1Pb 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=dPLBoIE3 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok" alt="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." title="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vera AO et al. PNAS DOI:10.1073/pnas.2426960122 </div> <div class="media-caption__description"> Images from an experiment using cells that produce green fluorescent protein (GFP, left panels). CRISPR-Cas9 disrupts GFP production (middle panels). LFN-Acr/PA, in turn, turns CRISPR-Cas9 off, allowing GFP production to resume (right panels). </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/621/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" 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field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/researchers-identify-molecules-rein-crispr-systems" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-molecules-rein-crispr-systems"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=aOIomzWh 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ" alt="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." title="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-molecules-rein-crispr-systems" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify molecules that rein in CRISPR systems</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The FDA’s recent approval of the first CRISPR-Cas9–based gene therapy marked a major milestone in biomedicine, validating genome editing as a promising treatment strategy for disorders like sickle cell disease, muscular dystrophy, and certain cancers.</p> <p>CRISPR-Cas9, often likened to “molecular scissors,” allows scientists to cut DNA at targeted sites to snip, repair, or replace genes. But despite its power, Cas9 poses a critical safety risk: the active enzyme can linger in cells and cause unintended DNA breaks—so-called off-target effects—which may trigger harmful mutations in healthy genes.</p> <p>Now, researchers in the labs of Ronald Raines and Amit Choudhary, both associate members in the ӳ����ý's <a href="/chemical-biology-and-therapeutics-science">Chemical Biology and Therapeutics Science Program</a>, have engineered a precise way to turn Cas9 off after its job is done—significantly reducing off-target effects and improving the clinical safety of gene editing. Their findings are detailed in the <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank"><i>Proceedings of the National Academy of Sciences</i> (<i>PNAS</i>)</a>.</p> <p>“To ‘turn off’ Cas9 after it achieves its intended genome-editing outcome, we developed the first cell-permeable anti-CRISPR protein system,” said Raines, who is the Roger and Georges Firmenich Professor of Natural Products Chemistry at MIT. “Our technology reduces the off-target activity of Cas9 and increases its genome-editing specificity and clinical utility.”</p> <p>The new tool — called LF<sub>N</sub>-Acr/PA — uses a protein-based delivery system to ferry anti-CRISPR proteins into human cells rapidly and efficiently. While natural Type II anti-CRISPR proteins (Acrs) are known to inhibit Cas9, their use in therapy has been limited: they’re often too bulky or charged to enter cells, and conventional delivery methods are too slow or ineffective.</p> <p>LF<sub>N</sub>-Acr/PA overcomes these hurdles using a component derived from anthrax toxin to introduce Acrs into cells within minutes. Even at picomolar concentrations, the system shuts down Cas9 activity with remarkable speed and precision—boosting genome-editing specificity up to 40%.</p> <p>MIT chemistry professor Bradley Pentelute, an expert on the anthrax delivery system, is also an author of the <i>PNAS</i> paper. Choudhary is an assistant professor of medicine at Harvard Medical School</p> <p>The implications of this advance are wide-ranging. With patent applications filed, LF<sub>N</sub>-Acr/PA represents a faster, safer, and more controllable means of harnessing CRISPR-Cas9, opening the door to more refined gene therapies with fewer unintended consequences.</p> <p><em>Adapted from <a href="https://chemistry.mit.edu/chemistry-news/a-boost-for-the-precision-of-genome-editing/" target="_blank">a story originally published by the MIT Department of Chemistry</a>.</em></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>Vera AO, et al. <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank">Protective antigen–mediated delivery of an anti-CRISPR protein for precision genome editing</a>. <i>PNAS</i>. Online August 4, 2025. DOI: 10.1073/pnas.2426960122.</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>The research was supported by the National Institutes of Health, the Merkin Institute for Transformative Technologies in Healthcare at the ӳ����ý, and a Gilliam Fellowship from the 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/chemical-biology-and-therapeutics-science" hreflang="en">Chemical Biology and Therapeutics Science Program</a></div> <div class="field__item"><a href="/broad-tags/crispr" hreflang="en">CRISPR</a></div> </div> </div> </div> </div> </div> Wed, 06 Aug 2025 19:06:44 +0000 tulrich@broadinstitute.org 5559251 at /news/scientists-engineer-crispr-enzymes-evade-immune-system <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists develop technology that brings new precision to genome editing</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-06T15:06:44-04:00" class="datetime">August 6, 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>Scientists develop technology that brings new precision to genome editing</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>Fast-acting, cell-permeable protein system that controls CRISPR-Cas9 could reduce off-target effects and advance gene therapy</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Danielle Doughty, MIT Department of Chemistry </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="2025-08-06T15:06:44-04:00" title="Wednesday, August 6, 2025 - 15:06" class="datetime">August 6, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=IvFcJmC1 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=64ear1Pb 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=dPLBoIE3 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok" alt="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." title="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vera AO et al. PNAS DOI:10.1073/pnas.2426960122 </div> <div class="media-caption__description"> Images from an experiment using cells that produce green fluorescent protein (GFP, left panels). CRISPR-Cas9 disrupts GFP production (middle panels). LFN-Acr/PA, in turn, turns CRISPR-Cas9 off, allowing GFP production to resume (right panels). </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/621/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" 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field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/researchers-identify-molecules-rein-crispr-systems" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-molecules-rein-crispr-systems"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=aOIomzWh 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ" alt="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." title="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-molecules-rein-crispr-systems" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify molecules that rein in CRISPR systems</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The FDA’s recent approval of the first CRISPR-Cas9–based gene therapy marked a major milestone in biomedicine, validating genome editing as a promising treatment strategy for disorders like sickle cell disease, muscular dystrophy, and certain cancers.</p> <p>CRISPR-Cas9, often likened to “molecular scissors,” allows scientists to cut DNA at targeted sites to snip, repair, or replace genes. But despite its power, Cas9 poses a critical safety risk: the active enzyme can linger in cells and cause unintended DNA breaks—so-called off-target effects—which may trigger harmful mutations in healthy genes.</p> <p>Now, researchers in the labs of Ronald Raines and Amit Choudhary, both associate members in the ӳ����ý's <a href="/chemical-biology-and-therapeutics-science">Chemical Biology and Therapeutics Science Program</a>, have engineered a precise way to turn Cas9 off after its job is done—significantly reducing off-target effects and improving the clinical safety of gene editing. Their findings are detailed in the <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank"><i>Proceedings of the National Academy of Sciences</i> (<i>PNAS</i>)</a>.</p> <p>“To ‘turn off’ Cas9 after it achieves its intended genome-editing outcome, we developed the first cell-permeable anti-CRISPR protein system,” said Raines, who is the Roger and Georges Firmenich Professor of Natural Products Chemistry at MIT. “Our technology reduces the off-target activity of Cas9 and increases its genome-editing specificity and clinical utility.”</p> <p>The new tool — called LF<sub>N</sub>-Acr/PA — uses a protein-based delivery system to ferry anti-CRISPR proteins into human cells rapidly and efficiently. While natural Type II anti-CRISPR proteins (Acrs) are known to inhibit Cas9, their use in therapy has been limited: they’re often too bulky or charged to enter cells, and conventional delivery methods are too slow or ineffective.</p> <p>LF<sub>N</sub>-Acr/PA overcomes these hurdles using a component derived from anthrax toxin to introduce Acrs into cells within minutes. Even at picomolar concentrations, the system shuts down Cas9 activity with remarkable speed and precision—boosting genome-editing specificity up to 40%.</p> <p>MIT chemistry professor Bradley Pentelute, an expert on the anthrax delivery system, is also an author of the <i>PNAS</i> paper. Choudhary is an assistant professor of medicine at Harvard Medical School</p> <p>The implications of this advance are wide-ranging. With patent applications filed, LF<sub>N</sub>-Acr/PA represents a faster, safer, and more controllable means of harnessing CRISPR-Cas9, opening the door to more refined gene therapies with fewer unintended consequences.</p> <p><em>Adapted from <a href="https://chemistry.mit.edu/chemistry-news/a-boost-for-the-precision-of-genome-editing/" target="_blank">a story originally published by the MIT Department of Chemistry</a>.</em></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>Vera AO, et al. <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank">Protective antigen–mediated delivery of an anti-CRISPR protein for precision genome editing</a>. <i>PNAS</i>. Online August 4, 2025. DOI: 10.1073/pnas.2426960122.</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>The research was supported by the National Institutes of Health, the Merkin Institute for Transformative Technologies in Healthcare at the ӳ����ý, and a Gilliam Fellowship from the 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/chemical-biology-and-therapeutics-science" hreflang="en">Chemical Biology and Therapeutics Science Program</a></div> <div class="field__item"><a href="/broad-tags/crispr" hreflang="en">CRISPR</a></div> </div> </div> </div> </div> </div> Thu, 09 Jan 2025 14:00:00 +0000 adicorat 5558021 at /news/some-crispr-screens-may-be-missing-cancer-drug-targets <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists develop technology that brings new precision to genome editing</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-06T15:06:44-04:00" class="datetime">August 6, 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>Scientists develop technology that brings new precision to genome editing</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>Fast-acting, cell-permeable protein system that controls CRISPR-Cas9 could reduce off-target effects and advance gene therapy</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Danielle Doughty, MIT Department of Chemistry </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="2025-08-06T15:06:44-04:00" title="Wednesday, August 6, 2025 - 15:06" class="datetime">August 6, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=IvFcJmC1 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=64ear1Pb 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=dPLBoIE3 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok" alt="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." title="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vera AO et al. PNAS DOI:10.1073/pnas.2426960122 </div> <div class="media-caption__description"> Images from an experiment using cells that produce green fluorescent protein (GFP, left panels). CRISPR-Cas9 disrupts GFP production (middle panels). LFN-Acr/PA, in turn, turns CRISPR-Cas9 off, allowing GFP production to resume (right panels). </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/621/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" 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field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related programs</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/chemical-biology-and-therapeutics-science">Chemical Biology and Therapeutics Science</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/researchers-identify-molecules-rein-crispr-systems" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-molecules-rein-crispr-systems"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=aOIomzWh 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ" alt="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." title="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-molecules-rein-crispr-systems" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify molecules that rein in CRISPR systems</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The FDA’s recent approval of the first CRISPR-Cas9–based gene therapy marked a major milestone in biomedicine, validating genome editing as a promising treatment strategy for disorders like sickle cell disease, muscular dystrophy, and certain cancers.</p> <p>CRISPR-Cas9, often likened to “molecular scissors,” allows scientists to cut DNA at targeted sites to snip, repair, or replace genes. But despite its power, Cas9 poses a critical safety risk: the active enzyme can linger in cells and cause unintended DNA breaks—so-called off-target effects—which may trigger harmful mutations in healthy genes.</p> <p>Now, researchers in the labs of Ronald Raines and Amit Choudhary, both associate members in the ӳ����ý's <a href="/chemical-biology-and-therapeutics-science">Chemical Biology and Therapeutics Science Program</a>, have engineered a precise way to turn Cas9 off after its job is done—significantly reducing off-target effects and improving the clinical safety of gene editing. Their findings are detailed in the <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank"><i>Proceedings of the National Academy of Sciences</i> (<i>PNAS</i>)</a>.</p> <p>“To ‘turn off’ Cas9 after it achieves its intended genome-editing outcome, we developed the first cell-permeable anti-CRISPR protein system,” said Raines, who is the Roger and Georges Firmenich Professor of Natural Products Chemistry at MIT. “Our technology reduces the off-target activity of Cas9 and increases its genome-editing specificity and clinical utility.”</p> <p>The new tool — called LF<sub>N</sub>-Acr/PA — uses a protein-based delivery system to ferry anti-CRISPR proteins into human cells rapidly and efficiently. While natural Type II anti-CRISPR proteins (Acrs) are known to inhibit Cas9, their use in therapy has been limited: they’re often too bulky or charged to enter cells, and conventional delivery methods are too slow or ineffective.</p> <p>LF<sub>N</sub>-Acr/PA overcomes these hurdles using a component derived from anthrax toxin to introduce Acrs into cells within minutes. Even at picomolar concentrations, the system shuts down Cas9 activity with remarkable speed and precision—boosting genome-editing specificity up to 40%.</p> <p>MIT chemistry professor Bradley Pentelute, an expert on the anthrax delivery system, is also an author of the <i>PNAS</i> paper. Choudhary is an assistant professor of medicine at Harvard Medical School</p> <p>The implications of this advance are wide-ranging. With patent applications filed, LF<sub>N</sub>-Acr/PA represents a faster, safer, and more controllable means of harnessing CRISPR-Cas9, opening the door to more refined gene therapies with fewer unintended consequences.</p> <p><em>Adapted from <a href="https://chemistry.mit.edu/chemistry-news/a-boost-for-the-precision-of-genome-editing/" target="_blank">a story originally published by the MIT Department of Chemistry</a>.</em></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>Vera AO, et al. <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank">Protective antigen–mediated delivery of an anti-CRISPR protein for precision genome editing</a>. <i>PNAS</i>. Online August 4, 2025. DOI: 10.1073/pnas.2426960122.</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>The research was supported by the National Institutes of Health, the Merkin Institute for Transformative Technologies in Healthcare at the ӳ����ý, and a Gilliam Fellowship from the 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/chemical-biology-and-therapeutics-science" hreflang="en">Chemical Biology and Therapeutics Science Program</a></div> <div class="field__item"><a href="/broad-tags/crispr" hreflang="en">CRISPR</a></div> </div> </div> </div> </div> </div> Fri, 14 Jun 2024 13:00:00 +0000 adicorat 5557016 at /news/study-reveals-links-between-blood-vessel-biology-and-heart-disease-risk <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists develop technology that brings new precision to genome editing</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-06T15:06:44-04:00" class="datetime">August 6, 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>Scientists develop technology that brings new precision to genome editing</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>Fast-acting, cell-permeable protein system that controls CRISPR-Cas9 could reduce off-target effects and advance gene therapy</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Danielle Doughty, MIT Department of Chemistry </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="2025-08-06T15:06:44-04:00" title="Wednesday, August 6, 2025 - 15:06" class="datetime">August 6, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=IvFcJmC1 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=64ear1Pb 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=dPLBoIE3 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok" alt="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." title="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vera AO et al. PNAS DOI:10.1073/pnas.2426960122 </div> <div class="media-caption__description"> Images from an experiment using cells that produce green fluorescent protein (GFP, left panels). CRISPR-Cas9 disrupts GFP production (middle panels). LFN-Acr/PA, in turn, turns CRISPR-Cas9 off, allowing GFP production to resume (right panels). </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/621/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" 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field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/researchers-identify-molecules-rein-crispr-systems" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-molecules-rein-crispr-systems"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=aOIomzWh 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ" alt="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." title="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-molecules-rein-crispr-systems" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify molecules that rein in CRISPR systems</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The FDA’s recent approval of the first CRISPR-Cas9–based gene therapy marked a major milestone in biomedicine, validating genome editing as a promising treatment strategy for disorders like sickle cell disease, muscular dystrophy, and certain cancers.</p> <p>CRISPR-Cas9, often likened to “molecular scissors,” allows scientists to cut DNA at targeted sites to snip, repair, or replace genes. But despite its power, Cas9 poses a critical safety risk: the active enzyme can linger in cells and cause unintended DNA breaks—so-called off-target effects—which may trigger harmful mutations in healthy genes.</p> <p>Now, researchers in the labs of Ronald Raines and Amit Choudhary, both associate members in the ӳ����ý's <a href="/chemical-biology-and-therapeutics-science">Chemical Biology and Therapeutics Science Program</a>, have engineered a precise way to turn Cas9 off after its job is done—significantly reducing off-target effects and improving the clinical safety of gene editing. Their findings are detailed in the <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank"><i>Proceedings of the National Academy of Sciences</i> (<i>PNAS</i>)</a>.</p> <p>“To ‘turn off’ Cas9 after it achieves its intended genome-editing outcome, we developed the first cell-permeable anti-CRISPR protein system,” said Raines, who is the Roger and Georges Firmenich Professor of Natural Products Chemistry at MIT. “Our technology reduces the off-target activity of Cas9 and increases its genome-editing specificity and clinical utility.”</p> <p>The new tool — called LF<sub>N</sub>-Acr/PA — uses a protein-based delivery system to ferry anti-CRISPR proteins into human cells rapidly and efficiently. While natural Type II anti-CRISPR proteins (Acrs) are known to inhibit Cas9, their use in therapy has been limited: they’re often too bulky or charged to enter cells, and conventional delivery methods are too slow or ineffective.</p> <p>LF<sub>N</sub>-Acr/PA overcomes these hurdles using a component derived from anthrax toxin to introduce Acrs into cells within minutes. Even at picomolar concentrations, the system shuts down Cas9 activity with remarkable speed and precision—boosting genome-editing specificity up to 40%.</p> <p>MIT chemistry professor Bradley Pentelute, an expert on the anthrax delivery system, is also an author of the <i>PNAS</i> paper. Choudhary is an assistant professor of medicine at Harvard Medical School</p> <p>The implications of this advance are wide-ranging. With patent applications filed, LF<sub>N</sub>-Acr/PA represents a faster, safer, and more controllable means of harnessing CRISPR-Cas9, opening the door to more refined gene therapies with fewer unintended consequences.</p> <p><em>Adapted from <a href="https://chemistry.mit.edu/chemistry-news/a-boost-for-the-precision-of-genome-editing/" target="_blank">a story originally published by the MIT Department of Chemistry</a>.</em></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>Vera AO, et al. <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank">Protective antigen–mediated delivery of an anti-CRISPR protein for precision genome editing</a>. <i>PNAS</i>. Online August 4, 2025. DOI: 10.1073/pnas.2426960122.</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>The research was supported by the National Institutes of Health, the Merkin Institute for Transformative Technologies in Healthcare at the ӳ����ý, and a Gilliam Fellowship from the 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/chemical-biology-and-therapeutics-science" hreflang="en">Chemical Biology and Therapeutics Science Program</a></div> <div class="field__item"><a href="/broad-tags/crispr" hreflang="en">CRISPR</a></div> </div> </div> </div> </div> </div> Wed, 07 Feb 2024 16:50:22 +0000 tulrich@broadinstitute.org 5556406 at /news/search-algorithm-reveals-nearly-200-new-kinds-crispr-systems <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists develop technology that brings new precision to genome editing</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-06T15:06:44-04:00" class="datetime">August 6, 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>Scientists develop technology that brings new precision to genome editing</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>Fast-acting, cell-permeable protein system that controls CRISPR-Cas9 could reduce off-target effects and advance gene therapy</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Danielle Doughty, MIT Department of Chemistry </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="2025-08-06T15:06:44-04:00" title="Wednesday, August 6, 2025 - 15:06" class="datetime">August 6, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=IvFcJmC1 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=64ear1Pb 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=dPLBoIE3 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok" alt="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." title="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vera AO et al. PNAS DOI:10.1073/pnas.2426960122 </div> <div class="media-caption__description"> Images from an experiment using cells that produce green fluorescent protein (GFP, left panels). CRISPR-Cas9 disrupts GFP production (middle panels). LFN-Acr/PA, in turn, turns CRISPR-Cas9 off, allowing GFP production to resume (right panels). </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/621/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" 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field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related programs</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/chemical-biology-and-therapeutics-science">Chemical Biology and Therapeutics Science</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/researchers-identify-molecules-rein-crispr-systems" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-molecules-rein-crispr-systems"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=aOIomzWh 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ" alt="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." title="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-molecules-rein-crispr-systems" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify molecules that rein in CRISPR systems</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The FDA’s recent approval of the first CRISPR-Cas9–based gene therapy marked a major milestone in biomedicine, validating genome editing as a promising treatment strategy for disorders like sickle cell disease, muscular dystrophy, and certain cancers.</p> <p>CRISPR-Cas9, often likened to “molecular scissors,” allows scientists to cut DNA at targeted sites to snip, repair, or replace genes. But despite its power, Cas9 poses a critical safety risk: the active enzyme can linger in cells and cause unintended DNA breaks—so-called off-target effects—which may trigger harmful mutations in healthy genes.</p> <p>Now, researchers in the labs of Ronald Raines and Amit Choudhary, both associate members in the ӳ����ý's <a href="/chemical-biology-and-therapeutics-science">Chemical Biology and Therapeutics Science Program</a>, have engineered a precise way to turn Cas9 off after its job is done—significantly reducing off-target effects and improving the clinical safety of gene editing. Their findings are detailed in the <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank"><i>Proceedings of the National Academy of Sciences</i> (<i>PNAS</i>)</a>.</p> <p>“To ‘turn off’ Cas9 after it achieves its intended genome-editing outcome, we developed the first cell-permeable anti-CRISPR protein system,” said Raines, who is the Roger and Georges Firmenich Professor of Natural Products Chemistry at MIT. “Our technology reduces the off-target activity of Cas9 and increases its genome-editing specificity and clinical utility.”</p> <p>The new tool — called LF<sub>N</sub>-Acr/PA — uses a protein-based delivery system to ferry anti-CRISPR proteins into human cells rapidly and efficiently. While natural Type II anti-CRISPR proteins (Acrs) are known to inhibit Cas9, their use in therapy has been limited: they’re often too bulky or charged to enter cells, and conventional delivery methods are too slow or ineffective.</p> <p>LF<sub>N</sub>-Acr/PA overcomes these hurdles using a component derived from anthrax toxin to introduce Acrs into cells within minutes. Even at picomolar concentrations, the system shuts down Cas9 activity with remarkable speed and precision—boosting genome-editing specificity up to 40%.</p> <p>MIT chemistry professor Bradley Pentelute, an expert on the anthrax delivery system, is also an author of the <i>PNAS</i> paper. Choudhary is an assistant professor of medicine at Harvard Medical School</p> <p>The implications of this advance are wide-ranging. With patent applications filed, LF<sub>N</sub>-Acr/PA represents a faster, safer, and more controllable means of harnessing CRISPR-Cas9, opening the door to more refined gene therapies with fewer unintended consequences.</p> <p><em>Adapted from <a href="https://chemistry.mit.edu/chemistry-news/a-boost-for-the-precision-of-genome-editing/" target="_blank">a story originally published by the MIT Department of Chemistry</a>.</em></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>Vera AO, et al. <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank">Protective antigen–mediated delivery of an anti-CRISPR protein for precision genome editing</a>. <i>PNAS</i>. Online August 4, 2025. DOI: 10.1073/pnas.2426960122.</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>The research was supported by the National Institutes of Health, the Merkin Institute for Transformative Technologies in Healthcare at the ӳ����ý, and a Gilliam Fellowship from the 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/chemical-biology-and-therapeutics-science" hreflang="en">Chemical Biology and Therapeutics Science Program</a></div> <div class="field__item"><a href="/broad-tags/crispr" hreflang="en">CRISPR</a></div> </div> </div> </div> </div> </div> Thu, 23 Nov 2023 19:00:00 +0000 adicorat 5556071 at /news/researchers-uncover-new-CRISPR-like-system-in-animals-that-can-edit-the-human-genome <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists develop technology that brings new precision to genome editing</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-06T15:06:44-04:00" class="datetime">August 6, 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>Scientists develop technology that brings new precision to genome editing</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>Fast-acting, cell-permeable protein system that controls CRISPR-Cas9 could reduce off-target effects and advance gene therapy</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Danielle Doughty, MIT Department of Chemistry </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="2025-08-06T15:06:44-04:00" title="Wednesday, August 6, 2025 - 15:06" class="datetime">August 6, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=IvFcJmC1 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=64ear1Pb 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=dPLBoIE3 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok" alt="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." title="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vera AO et al. PNAS DOI:10.1073/pnas.2426960122 </div> <div class="media-caption__description"> Images from an experiment using cells that produce green fluorescent protein (GFP, left panels). CRISPR-Cas9 disrupts GFP production (middle panels). LFN-Acr/PA, in turn, turns CRISPR-Cas9 off, allowing GFP production to resume (right panels). </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/621/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" 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field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/researchers-identify-molecules-rein-crispr-systems" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-molecules-rein-crispr-systems"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=aOIomzWh 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ" alt="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." title="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-molecules-rein-crispr-systems" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify molecules that rein in CRISPR systems</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The FDA’s recent approval of the first CRISPR-Cas9–based gene therapy marked a major milestone in biomedicine, validating genome editing as a promising treatment strategy for disorders like sickle cell disease, muscular dystrophy, and certain cancers.</p> <p>CRISPR-Cas9, often likened to “molecular scissors,” allows scientists to cut DNA at targeted sites to snip, repair, or replace genes. But despite its power, Cas9 poses a critical safety risk: the active enzyme can linger in cells and cause unintended DNA breaks—so-called off-target effects—which may trigger harmful mutations in healthy genes.</p> <p>Now, researchers in the labs of Ronald Raines and Amit Choudhary, both associate members in the ӳ����ý's <a href="/chemical-biology-and-therapeutics-science">Chemical Biology and Therapeutics Science Program</a>, have engineered a precise way to turn Cas9 off after its job is done—significantly reducing off-target effects and improving the clinical safety of gene editing. Their findings are detailed in the <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank"><i>Proceedings of the National Academy of Sciences</i> (<i>PNAS</i>)</a>.</p> <p>“To ‘turn off’ Cas9 after it achieves its intended genome-editing outcome, we developed the first cell-permeable anti-CRISPR protein system,” said Raines, who is the Roger and Georges Firmenich Professor of Natural Products Chemistry at MIT. “Our technology reduces the off-target activity of Cas9 and increases its genome-editing specificity and clinical utility.”</p> <p>The new tool — called LF<sub>N</sub>-Acr/PA — uses a protein-based delivery system to ferry anti-CRISPR proteins into human cells rapidly and efficiently. While natural Type II anti-CRISPR proteins (Acrs) are known to inhibit Cas9, their use in therapy has been limited: they’re often too bulky or charged to enter cells, and conventional delivery methods are too slow or ineffective.</p> <p>LF<sub>N</sub>-Acr/PA overcomes these hurdles using a component derived from anthrax toxin to introduce Acrs into cells within minutes. Even at picomolar concentrations, the system shuts down Cas9 activity with remarkable speed and precision—boosting genome-editing specificity up to 40%.</p> <p>MIT chemistry professor Bradley Pentelute, an expert on the anthrax delivery system, is also an author of the <i>PNAS</i> paper. Choudhary is an assistant professor of medicine at Harvard Medical School</p> <p>The implications of this advance are wide-ranging. With patent applications filed, LF<sub>N</sub>-Acr/PA represents a faster, safer, and more controllable means of harnessing CRISPR-Cas9, opening the door to more refined gene therapies with fewer unintended consequences.</p> <p><em>Adapted from <a href="https://chemistry.mit.edu/chemistry-news/a-boost-for-the-precision-of-genome-editing/" target="_blank">a story originally published by the MIT Department of Chemistry</a>.</em></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>Vera AO, et al. <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank">Protective antigen–mediated delivery of an anti-CRISPR protein for precision genome editing</a>. <i>PNAS</i>. Online August 4, 2025. DOI: 10.1073/pnas.2426960122.</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>The research was supported by the National Institutes of Health, the Merkin Institute for Transformative Technologies in Healthcare at the ӳ����ý, and a Gilliam Fellowship from the 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/chemical-biology-and-therapeutics-science" hreflang="en">Chemical Biology and Therapeutics Science Program</a></div> <div class="field__item"><a href="/broad-tags/crispr" hreflang="en">CRISPR</a></div> </div> </div> </div> </div> </div> Wed, 28 Jun 2023 15:00:11 +0000 leah@broadinstitute.org 1282401 at /news/prime-editing-shows-proof-concept-treating-sickle-cell-disease <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists develop technology that brings new precision to genome editing</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-06T15:06:44-04:00" class="datetime">August 6, 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>Scientists develop technology that brings new precision to genome editing</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>Fast-acting, cell-permeable protein system that controls CRISPR-Cas9 could reduce off-target effects and advance gene therapy</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Danielle Doughty, MIT Department of Chemistry </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="2025-08-06T15:06:44-04:00" title="Wednesday, August 6, 2025 - 15:06" class="datetime">August 6, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=IvFcJmC1 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=64ear1Pb 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=dPLBoIE3 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok" alt="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." title="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vera AO et al. PNAS DOI:10.1073/pnas.2426960122 </div> <div class="media-caption__description"> Images from an experiment using cells that produce green fluorescent protein (GFP, left panels). CRISPR-Cas9 disrupts GFP production (middle panels). LFN-Acr/PA, in turn, turns CRISPR-Cas9 off, allowing GFP production to resume (right panels). </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/621/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" 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field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related programs</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/chemical-biology-and-therapeutics-science">Chemical Biology and Therapeutics Science</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/researchers-identify-molecules-rein-crispr-systems" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-molecules-rein-crispr-systems"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=aOIomzWh 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ" alt="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." title="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-molecules-rein-crispr-systems" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify molecules that rein in CRISPR systems</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The FDA’s recent approval of the first CRISPR-Cas9–based gene therapy marked a major milestone in biomedicine, validating genome editing as a promising treatment strategy for disorders like sickle cell disease, muscular dystrophy, and certain cancers.</p> <p>CRISPR-Cas9, often likened to “molecular scissors,” allows scientists to cut DNA at targeted sites to snip, repair, or replace genes. But despite its power, Cas9 poses a critical safety risk: the active enzyme can linger in cells and cause unintended DNA breaks—so-called off-target effects—which may trigger harmful mutations in healthy genes.</p> <p>Now, researchers in the labs of Ronald Raines and Amit Choudhary, both associate members in the ӳ����ý's <a href="/chemical-biology-and-therapeutics-science">Chemical Biology and Therapeutics Science Program</a>, have engineered a precise way to turn Cas9 off after its job is done—significantly reducing off-target effects and improving the clinical safety of gene editing. Their findings are detailed in the <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank"><i>Proceedings of the National Academy of Sciences</i> (<i>PNAS</i>)</a>.</p> <p>“To ‘turn off’ Cas9 after it achieves its intended genome-editing outcome, we developed the first cell-permeable anti-CRISPR protein system,” said Raines, who is the Roger and Georges Firmenich Professor of Natural Products Chemistry at MIT. “Our technology reduces the off-target activity of Cas9 and increases its genome-editing specificity and clinical utility.”</p> <p>The new tool — called LF<sub>N</sub>-Acr/PA — uses a protein-based delivery system to ferry anti-CRISPR proteins into human cells rapidly and efficiently. While natural Type II anti-CRISPR proteins (Acrs) are known to inhibit Cas9, their use in therapy has been limited: they’re often too bulky or charged to enter cells, and conventional delivery methods are too slow or ineffective.</p> <p>LF<sub>N</sub>-Acr/PA overcomes these hurdles using a component derived from anthrax toxin to introduce Acrs into cells within minutes. Even at picomolar concentrations, the system shuts down Cas9 activity with remarkable speed and precision—boosting genome-editing specificity up to 40%.</p> <p>MIT chemistry professor Bradley Pentelute, an expert on the anthrax delivery system, is also an author of the <i>PNAS</i> paper. Choudhary is an assistant professor of medicine at Harvard Medical School</p> <p>The implications of this advance are wide-ranging. With patent applications filed, LF<sub>N</sub>-Acr/PA represents a faster, safer, and more controllable means of harnessing CRISPR-Cas9, opening the door to more refined gene therapies with fewer unintended consequences.</p> <p><em>Adapted from <a href="https://chemistry.mit.edu/chemistry-news/a-boost-for-the-precision-of-genome-editing/" target="_blank">a story originally published by the MIT Department of Chemistry</a>.</em></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>Vera AO, et al. <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank">Protective antigen–mediated delivery of an anti-CRISPR protein for precision genome editing</a>. <i>PNAS</i>. Online August 4, 2025. DOI: 10.1073/pnas.2426960122.</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>The research was supported by the National Institutes of Health, the Merkin Institute for Transformative Technologies in Healthcare at the ӳ����ý, and a Gilliam Fellowship from the 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/chemical-biology-and-therapeutics-science" hreflang="en">Chemical Biology and Therapeutics Science Program</a></div> <div class="field__item"><a href="/broad-tags/crispr" hreflang="en">CRISPR</a></div> </div> </div> </div> </div> </div> Mon, 17 Apr 2023 15:53:54 +0000 kzusi@broadinstitute.org 1282061 at /news/scientists-unveil-functional-landscape-essential-genes <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists develop technology that brings new precision to genome editing</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-06T15:06:44-04:00" class="datetime">August 6, 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>Scientists develop technology that brings new precision to genome editing</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>Fast-acting, cell-permeable protein system that controls CRISPR-Cas9 could reduce off-target effects and advance gene therapy</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Danielle Doughty, MIT Department of Chemistry </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="2025-08-06T15:06:44-04:00" title="Wednesday, August 6, 2025 - 15:06" class="datetime">August 6, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=IvFcJmC1 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=64ear1Pb 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=dPLBoIE3 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok" alt="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." title="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vera AO et al. PNAS DOI:10.1073/pnas.2426960122 </div> <div class="media-caption__description"> Images from an experiment using cells that produce green fluorescent protein (GFP, left panels). CRISPR-Cas9 disrupts GFP production (middle panels). LFN-Acr/PA, in turn, turns CRISPR-Cas9 off, allowing GFP production to resume (right panels). </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/621/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" 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field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/researchers-identify-molecules-rein-crispr-systems" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-molecules-rein-crispr-systems"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=aOIomzWh 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ" alt="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." title="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-molecules-rein-crispr-systems" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify molecules that rein in CRISPR systems</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The FDA’s recent approval of the first CRISPR-Cas9–based gene therapy marked a major milestone in biomedicine, validating genome editing as a promising treatment strategy for disorders like sickle cell disease, muscular dystrophy, and certain cancers.</p> <p>CRISPR-Cas9, often likened to “molecular scissors,” allows scientists to cut DNA at targeted sites to snip, repair, or replace genes. But despite its power, Cas9 poses a critical safety risk: the active enzyme can linger in cells and cause unintended DNA breaks—so-called off-target effects—which may trigger harmful mutations in healthy genes.</p> <p>Now, researchers in the labs of Ronald Raines and Amit Choudhary, both associate members in the ӳ����ý's <a href="/chemical-biology-and-therapeutics-science">Chemical Biology and Therapeutics Science Program</a>, have engineered a precise way to turn Cas9 off after its job is done—significantly reducing off-target effects and improving the clinical safety of gene editing. Their findings are detailed in the <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank"><i>Proceedings of the National Academy of Sciences</i> (<i>PNAS</i>)</a>.</p> <p>“To ‘turn off’ Cas9 after it achieves its intended genome-editing outcome, we developed the first cell-permeable anti-CRISPR protein system,” said Raines, who is the Roger and Georges Firmenich Professor of Natural Products Chemistry at MIT. “Our technology reduces the off-target activity of Cas9 and increases its genome-editing specificity and clinical utility.”</p> <p>The new tool — called LF<sub>N</sub>-Acr/PA — uses a protein-based delivery system to ferry anti-CRISPR proteins into human cells rapidly and efficiently. While natural Type II anti-CRISPR proteins (Acrs) are known to inhibit Cas9, their use in therapy has been limited: they’re often too bulky or charged to enter cells, and conventional delivery methods are too slow or ineffective.</p> <p>LF<sub>N</sub>-Acr/PA overcomes these hurdles using a component derived from anthrax toxin to introduce Acrs into cells within minutes. Even at picomolar concentrations, the system shuts down Cas9 activity with remarkable speed and precision—boosting genome-editing specificity up to 40%.</p> <p>MIT chemistry professor Bradley Pentelute, an expert on the anthrax delivery system, is also an author of the <i>PNAS</i> paper. Choudhary is an assistant professor of medicine at Harvard Medical School</p> <p>The implications of this advance are wide-ranging. With patent applications filed, LF<sub>N</sub>-Acr/PA represents a faster, safer, and more controllable means of harnessing CRISPR-Cas9, opening the door to more refined gene therapies with fewer unintended consequences.</p> <p><em>Adapted from <a href="https://chemistry.mit.edu/chemistry-news/a-boost-for-the-precision-of-genome-editing/" target="_blank">a story originally published by the MIT Department of Chemistry</a>.</em></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>Vera AO, et al. <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank">Protective antigen–mediated delivery of an anti-CRISPR protein for precision genome editing</a>. <i>PNAS</i>. Online August 4, 2025. DOI: 10.1073/pnas.2426960122.</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>The research was supported by the National Institutes of Health, the Merkin Institute for Transformative Technologies in Healthcare at the ӳ����ý, and a Gilliam Fellowship from the 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/chemical-biology-and-therapeutics-science" hreflang="en">Chemical Biology and Therapeutics Science Program</a></div> <div class="field__item"><a href="/broad-tags/crispr" hreflang="en">CRISPR</a></div> </div> </div> </div> </div> </div> Mon, 07 Nov 2022 16:05:51 +0000 tulrich@broadinstitute.org 1245906 at /news/broad-discovery-center-cambridge-opens-public-october <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists develop technology that brings new precision to genome editing</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-06T15:06:44-04:00" class="datetime">August 6, 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>Scientists develop technology that brings new precision to genome editing</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>Fast-acting, cell-permeable protein system that controls CRISPR-Cas9 could reduce off-target effects and advance gene therapy</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Danielle Doughty, MIT Department of Chemistry </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="2025-08-06T15:06:44-04:00" title="Wednesday, August 6, 2025 - 15:06" class="datetime">August 6, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=IvFcJmC1 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=64ear1Pb 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=dPLBoIE3 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok" alt="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." title="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vera AO et al. PNAS DOI:10.1073/pnas.2426960122 </div> <div class="media-caption__description"> Images from an experiment using cells that produce green fluorescent protein (GFP, left panels). CRISPR-Cas9 disrupts GFP production (middle panels). LFN-Acr/PA, in turn, turns CRISPR-Cas9 off, allowing GFP production to resume (right panels). </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/621/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" 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srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=aOIomzWh 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ" alt="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." title="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-molecules-rein-crispr-systems" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify molecules that rein in CRISPR systems</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The FDA’s recent approval of the first CRISPR-Cas9–based gene therapy marked a major milestone in biomedicine, validating genome editing as a promising treatment strategy for disorders like sickle cell disease, muscular dystrophy, and certain cancers.</p> <p>CRISPR-Cas9, often likened to “molecular scissors,” allows scientists to cut DNA at targeted sites to snip, repair, or replace genes. But despite its power, Cas9 poses a critical safety risk: the active enzyme can linger in cells and cause unintended DNA breaks—so-called off-target effects—which may trigger harmful mutations in healthy genes.</p> <p>Now, researchers in the labs of Ronald Raines and Amit Choudhary, both associate members in the ӳ����ý's <a href="/chemical-biology-and-therapeutics-science">Chemical Biology and Therapeutics Science Program</a>, have engineered a precise way to turn Cas9 off after its job is done—significantly reducing off-target effects and improving the clinical safety of gene editing. Their findings are detailed in the <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank"><i>Proceedings of the National Academy of Sciences</i> (<i>PNAS</i>)</a>.</p> <p>“To ‘turn off’ Cas9 after it achieves its intended genome-editing outcome, we developed the first cell-permeable anti-CRISPR protein system,” said Raines, who is the Roger and Georges Firmenich Professor of Natural Products Chemistry at MIT. “Our technology reduces the off-target activity of Cas9 and increases its genome-editing specificity and clinical utility.”</p> <p>The new tool — called LF<sub>N</sub>-Acr/PA — uses a protein-based delivery system to ferry anti-CRISPR proteins into human cells rapidly and efficiently. While natural Type II anti-CRISPR proteins (Acrs) are known to inhibit Cas9, their use in therapy has been limited: they’re often too bulky or charged to enter cells, and conventional delivery methods are too slow or ineffective.</p> <p>LF<sub>N</sub>-Acr/PA overcomes these hurdles using a component derived from anthrax toxin to introduce Acrs into cells within minutes. Even at picomolar concentrations, the system shuts down Cas9 activity with remarkable speed and precision—boosting genome-editing specificity up to 40%.</p> <p>MIT chemistry professor Bradley Pentelute, an expert on the anthrax delivery system, is also an author of the <i>PNAS</i> paper. Choudhary is an assistant professor of medicine at Harvard Medical School</p> <p>The implications of this advance are wide-ranging. With patent applications filed, LF<sub>N</sub>-Acr/PA represents a faster, safer, and more controllable means of harnessing CRISPR-Cas9, opening the door to more refined gene therapies with fewer unintended consequences.</p> <p><em>Adapted from <a href="https://chemistry.mit.edu/chemistry-news/a-boost-for-the-precision-of-genome-editing/" target="_blank">a story originally published by the MIT Department of Chemistry</a>.</em></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>Vera AO, et al. <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank">Protective antigen–mediated delivery of an anti-CRISPR protein for precision genome editing</a>. <i>PNAS</i>. Online August 4, 2025. DOI: 10.1073/pnas.2426960122.</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>The research was supported by the National Institutes of Health, the Merkin Institute for Transformative Technologies in Healthcare at the ӳ����ý, and a Gilliam Fellowship from the 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/chemical-biology-and-therapeutics-science" hreflang="en">Chemical Biology and Therapeutics Science Program</a></div> <div class="field__item"><a href="/broad-tags/crispr" hreflang="en">CRISPR</a></div> </div> </div> </div> </div> </div> Mon, 19 Sep 2022 14:53:09 +0000 kzusi@broadinstitute.org 1195701 at /news/researchers-use-crispr-build-melanoma-models-scratch-using-human-cells <span class="field field--name-title field--type-string field--label-hidden"><h1>Scientists develop technology that brings new precision to genome editing</h1> </span> <span class="field field--name-uid field--type-entity-reference field--label-hidden"> <span>By Tom Ulrich</span> </span> <span class="field field--name-created field--type-created field--label-hidden"><time datetime="2025-08-06T15:06:44-04:00" class="datetime">August 6, 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>Scientists develop technology that brings new precision to genome editing</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>Fast-acting, cell-permeable protein system that controls CRISPR-Cas9 could reduce off-target effects and advance gene therapy</p> </div> </div> </div> <div class="hero-section__author"> <div class="block block-layout-builder block-extra-field-blocknodelong-storyextra-field-author-custom"> By Danielle Doughty, MIT Department of Chemistry </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="2025-08-06T15:06:44-04:00" title="Wednesday, August 6, 2025 - 15:06" class="datetime">August 6, 2025</time> </span> </div> </div> </div> <div class="hero-section__right col-6"> <div class="hero-section__image"> <div class="block block-layout-builder block-field-blocknodelong-storyfield-image"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"> <article class="media media--type-image media--view-mode-multiple-content-types-header"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <picture> <source srcset="/files/styles/multiple_ct_header_desktop_xl/public/longstory/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=Z7U2f80W 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=IvFcJmC1 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=64ear1Pb 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=dPLBoIE3 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok 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/%20cas9%20inhibition%20by%20Acrs%20in%20cells%20pnas.2426960122fig02.png?h=ae0fde30&itok=LfIYDAok" alt="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." title="A set of fluorescent microscopy images depicting green and blue cells, showing the effects of inhibiting CRISPR-Cas9 using anti-CRISPR proteins delivered with LFN-Acr/PA." typeof="foaf:Image" /> </picture> </div> <div class="media-caption"> <div class="media-caption__credit"> Credit: Vera AO et al. PNAS DOI:10.1073/pnas.2426960122 </div> <div class="media-caption__description"> Images from an experiment using cells that produce green fluorescent protein (GFP, left panels). CRISPR-Cas9 disrupts GFP production (middle panels). LFN-Acr/PA, in turn, turns CRISPR-Cas9 off, allowing GFP production to resume (right panels). </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/621/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" 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field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--text-with-sidebar text-with-sidebar"> <div class="field field--name-field-sidebar field--type-entity-reference-revisions field--label-hidden field__items"> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-menu sidebar-menu"> <div class="sidebar-menu__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related programs</p> </div> <div class="field field--name-field-links field--type-link field--label-hidden field__items"> <div class="field__item"><a href="/chemical-biology-and-therapeutics-science">Chemical Biology and Therapeutics Science</a></div> </div> </div> </div> </div> <div class="field__item"> <div class="paragraph paragraph--type--sidebar-articles sidebar-articles"> <div class="sidebar-articles__col"> <div class="clearfix text-formatted field field--name-field-heading field--type-text field--label-hidden field__item"><p>Related news</p> </div> <div class="field field--name-field-content-reference field--type-entity-reference field--label-hidden field__items"> <div class="field__item"><article about="/news/researchers-identify-molecules-rein-crispr-systems" class="node"> <div class="field field--name-field-image field--type-entity-reference field--label-hidden field__item"><article class="media media--type-image media--view-mode-multiple-ct-sidebar-link-with-image"> <div class="field field--name-field-media-image field--type-image field--label-hidden field__item"> <a href="/news/researchers-identify-molecules-rein-crispr-systems"><picture> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1921px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop_xl/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=f3nzDr77 1x" media="all and (min-width: 1601px) and (max-width: 1920px)" type="image/jpeg" width="104" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 1340px) and (max-width: 1600px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_desktop/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=8EQmzLxH 1x" media="all and (min-width: 800px) and (max-width: 1339px)" type="image/jpeg" width="87" height="104"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_tablet/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=aOIomzWh 1x" media="all and (min-width: 540px) and (max-width: 799px)" type="image/jpeg" width="285" height="186"/> <source srcset="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ 1x" media="all and (max-width: 539px)" type="image/jpeg" width="220" height="186"/> <img loading="eager" width="220" height="186" src="/files/styles/multiple_ct_sidebar_link_with_image_phone/public/news/images/2019/NewsStory_CRISPR-blocker.jpg?h=d3e04ee7&itok=dUTcpofJ" alt="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." title="Left: CRISPR-Cas9 enzymes knock out the gene that makes the cells green. Right: Small-molecule inhibitors block the CRISPR-Cas9 enzyme action, preventing gene knockout and keeping the cells green." typeof="foaf:Image" /> </picture></a> </div> </article> </div> <div class="node__content"> <a href="/news/researchers-identify-molecules-rein-crispr-systems" class="node__title"><span class="field field--name-title field--type-string field--label-hidden">Researchers identify molecules that rein in CRISPR systems</span> </a> </div> </article> </div> </div> </div> </div> </div> </div> <div class="clearfix text-formatted field field--name-field-text field--type-text-long field--label-hidden field__item"><p>The FDA’s recent approval of the first CRISPR-Cas9–based gene therapy marked a major milestone in biomedicine, validating genome editing as a promising treatment strategy for disorders like sickle cell disease, muscular dystrophy, and certain cancers.</p> <p>CRISPR-Cas9, often likened to “molecular scissors,” allows scientists to cut DNA at targeted sites to snip, repair, or replace genes. But despite its power, Cas9 poses a critical safety risk: the active enzyme can linger in cells and cause unintended DNA breaks—so-called off-target effects—which may trigger harmful mutations in healthy genes.</p> <p>Now, researchers in the labs of Ronald Raines and Amit Choudhary, both associate members in the ӳ����ý's <a href="/chemical-biology-and-therapeutics-science">Chemical Biology and Therapeutics Science Program</a>, have engineered a precise way to turn Cas9 off after its job is done—significantly reducing off-target effects and improving the clinical safety of gene editing. Their findings are detailed in the <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank"><i>Proceedings of the National Academy of Sciences</i> (<i>PNAS</i>)</a>.</p> <p>“To ‘turn off’ Cas9 after it achieves its intended genome-editing outcome, we developed the first cell-permeable anti-CRISPR protein system,” said Raines, who is the Roger and Georges Firmenich Professor of Natural Products Chemistry at MIT. “Our technology reduces the off-target activity of Cas9 and increases its genome-editing specificity and clinical utility.”</p> <p>The new tool — called LF<sub>N</sub>-Acr/PA — uses a protein-based delivery system to ferry anti-CRISPR proteins into human cells rapidly and efficiently. While natural Type II anti-CRISPR proteins (Acrs) are known to inhibit Cas9, their use in therapy has been limited: they’re often too bulky or charged to enter cells, and conventional delivery methods are too slow or ineffective.</p> <p>LF<sub>N</sub>-Acr/PA overcomes these hurdles using a component derived from anthrax toxin to introduce Acrs into cells within minutes. Even at picomolar concentrations, the system shuts down Cas9 activity with remarkable speed and precision—boosting genome-editing specificity up to 40%.</p> <p>MIT chemistry professor Bradley Pentelute, an expert on the anthrax delivery system, is also an author of the <i>PNAS</i> paper. Choudhary is an assistant professor of medicine at Harvard Medical School</p> <p>The implications of this advance are wide-ranging. With patent applications filed, LF<sub>N</sub>-Acr/PA represents a faster, safer, and more controllable means of harnessing CRISPR-Cas9, opening the door to more refined gene therapies with fewer unintended consequences.</p> <p><em>Adapted from <a href="https://chemistry.mit.edu/chemistry-news/a-boost-for-the-precision-of-genome-editing/" target="_blank">a story originally published by the MIT Department of Chemistry</a>.</em></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>Vera AO, et al. <a href="https://www.pnas.org/doi/10.1073/pnas.2426960122" target="_blank">Protective antigen–mediated delivery of an anti-CRISPR protein for precision genome editing</a>. <i>PNAS</i>. Online August 4, 2025. DOI: 10.1073/pnas.2426960122.</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>The research was supported by the National Institutes of Health, the Merkin Institute for Transformative Technologies in Healthcare at the ӳ����ý, and a Gilliam Fellowship from the 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/chemical-biology-and-therapeutics-science" hreflang="en">Chemical Biology and Therapeutics Science Program</a></div> <div class="field__item"><a href="/broad-tags/crispr" hreflang="en">CRISPR</a></div> </div> </div> </div> </div> </div> Thu, 28 Apr 2022 18:01:31 +0000 adicorat 1130946 at