{"id":83279,"date":"2025-08-20T20:41:06","date_gmt":"2025-08-20T20:41:06","guid":{"rendered":"https:\/\/www.newsbeep.com\/au\/83279\/"},"modified":"2025-08-20T20:41:06","modified_gmt":"2025-08-20T20:41:06","slug":"a-boost-for-the-precision-of-genome-editing-mit-news","status":"publish","type":"post","link":"https:\/\/www.newsbeep.com\/au\/83279\/","title":{"rendered":"A boost for the precision of genome editing | MIT News"},"content":{"rendered":"

The U.S. Food and Drug Administration\u2019s recent approval of the first CRISPR-Cas9\u2013based gene therapy<\/a> has 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>\n

CRISPR-Cas9, often likened to \u201cmolecular scissors,\u201d 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 \u2014 so-called off-target effects \u2014 which may trigger harmful mutations in healthy genes.<\/p>\n

Now, researchers in the labs of Ronald T. Raines<\/a>, MIT professor of chemistry, and Amit Choudhary, professor of medicine at Harvard Medical School, have engineered a precise way to turn Cas9 off after its job is done \u2014 significantly reducing off-target effects and improving the clinical safety of gene editing. Their findings are detailed in a new paper published in the\u00a0Proceedings of the National Academy of Sciences<\/a> (PNAS).<\/p>\n

\u201cTo \u2018turn off\u2019 Cas9 after it achieves its intended genome-editing outcome, we developed the first cell-permeable anti-CRISPR protein system,\u201d says Raines, the Roger and Georges Firmenich Professor of Natural Products Chemistry. \u201cOur technology reduces the off-target activity of Cas9 and increases its genome-editing specificity and clinical utility.\u201d<\/p>\n

The new tool \u2014 called LFN-Acr\/PA \u2014 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 because they\u2019re often too bulky or charged to enter cells, and conventional delivery methods are too slow or ineffective.<\/p>\n

LFN-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 \u2014 boosting genome-editing specificity up to 40 percent.<\/p>\n

Bradley L. Pentelute<\/a>, MIT professor of chemistry, is an expert on the anthrax delivery system, and is also an author of the paper.<\/p>\n

The implications of this advance are wide-ranging. With patent applications filed, LFN-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>\n

The research was supported by the National Institutes of Health and a Gilliam Fellowship from the Howard Hughes Medical Institute awarded to lead author Axel O. Vera, a graduate student in the Department of Chemistry.<\/p>\n","protected":false},"excerpt":{"rendered":"The U.S. Food and Drug Administration\u2019s recent approval of the first CRISPR-Cas9\u2013based gene therapy has marked a major…\n","protected":false},"author":2,"featured_media":83280,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[62778,62775,64,63,62777,62773,137,62774,62772,62776],"class_list":{"0":"post-83279","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-health","8":"tag-amit-choudhary","9":"tag-anthrax-toxin","10":"tag-au","11":"tag-australia","12":"tag-brad-pentelute","13":"tag-crispr-cas9","14":"tag-health","15":"tag-lfn-acr-pa","16":"tag-mit-chemistry","17":"tag-ronald-raines"},"_links":{"self":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/posts\/83279","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/comments?post=83279"}],"version-history":[{"count":0,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/posts\/83279\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/media\/83280"}],"wp:attachment":[{"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/media?parent=83279"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/categories?post=83279"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.newsbeep.com\/au\/wp-json\/wp\/v2\/tags?post=83279"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}