{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T19:03:03Z","timestamp":1789758183522,"version":"4.0.1"},"reference-count":74,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"12","funder":[{"name":"SLS-Qidong Innovation Fund"}],"content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Adv."],"published-print":{"date-parts":[[2026,3,20]]},"abstract":"<jats:p>\n                    Huntington\u2019s disease (HD) is a monogenic autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in exon 1 of the\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    gene, yielding a gain-of-toxic-function mutant Huntingtin protein (mHTT). CRISPR-Cas9 is a potentially powerful therapeutic strategy for HD by eliminating mutant\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    (m\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    ) gene. We developed a specific SaCas9 guide RNA to target human m\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    and a self-inactivating gene editing system that abolishes SaCas9 after a short transient expression for high gene editing efficiency and maximal safety to prevent off-target effects. Both conventional and the self-inactivating gene editing systems successfully eliminated m\n                    <jats:italic toggle=\"yes\">HTT<\/jats:italic>\n                    gene, 60 to 90% mHTT protein and 90% of mHTT aggregation in BAC226Q mouse brains, which resulted in significant long-term rescue of neuropathology, motor deficits, weight loss, and shortened life span. These beneficial effects were observed when gene editing was applied before, at, and well after the onset of pathological and behavioral abnormalities. These proof-of-concept data demonstrate that gene editing can be a highly effective therapeutic approach for HD.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea8052","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:59:43Z","timestamp":1773856783000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":2,"title":["Self-inactivating AAV-CRISPR at different ages enables sustained amelioration of Huntington\u2019s disease deficits in BAC226Q mice"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-0661-4902","authenticated-orcid":true,"given":"Yuanyi","family":"Dai","sequence":"first","affiliation":[{"name":"The MOE Key Laboratory of Cell Proliferation and Differentiation, School of Life Sciences, Peking University, Beijing 100871, 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