{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T03:24:36Z","timestamp":1771817076720,"version":"3.50.1"},"reference-count":17,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T00:00:00Z","timestamp":1719187200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech &amp;amp; Bioengineering"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Spinal muscular atrophy (SMA) is a devastating neuromuscular disease caused by mutations in the survival motor neuron 1 (<jats:italic>SMN1<\/jats:italic>) gene. Gene editing technology repairs the conversion of the 6th base T to C in exon 7 of the paralogous <jats:italic>SMN2<\/jats:italic> gene, compensating for the SMN protein expression and promoting the survival and function of motor neurons. However, low editing efficiency and unintended off\u2010target effects limit the application of this technology. Here, we optimized a TaC9\u2010adenine base editor (ABE) system by combining Cas9 nickase with the transcription activator\u2010like effector (TALE)\u2010adenosine deaminase fusion protein to effectively and precisely edit <jats:italic>SMN2<\/jats:italic> without detectable Cas9 dependent off\u2010target effects in human cell lines. We also generated human SMA\u2010induced pluripotent stem cells (SMA\u2010iPSCs) through the mutation of the splice acceptor or deletion of the exon 7 of <jats:italic>SMN1<\/jats:italic>. TaC9\u2010R10 induced 45% <jats:italic>SMN2<\/jats:italic> T6\u2009&gt;\u2009C conversion in the SMA\u2010iPSCs. The <jats:italic>SMN2<\/jats:italic> T6\u2009&gt;\u2009C splice\u2010corrected SMA\u2010iPSCs were directionally differentiated into motor neurons, exhibiting SMN protein recovery and antiapoptosis ability. Therefore, the TaC9\u2010ABE system with dual guides from the combination of Cas9 with TALE could be a potential therapeutic strategy for SMA with high efficacy and safety.<\/jats:p>","DOI":"10.1002\/bit.28780","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T01:39:30Z","timestamp":1719279570000},"page":"3059-3067","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Improvement of TaC9\u2010ABE mediated correction of human <i>SMN2<\/i> gene"],"prefix":"10.1002","volume":"121","author":[{"given":"Xiaohua","family":"Peng","sequence":"first","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, South China Institute of Large Animal Models for Biomedicine Wuyi University Jiangmen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Chi","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, South China Institute of Large Animal Models for Biomedicine Wuyi University Jiangmen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinling","family":"Wang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, South China Institute of Large Animal Models for Biomedicine Wuyi University Jiangmen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuangpeng","family":"Li","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Large Animal Models for Biomedicine, South China Institute of Large Animal Models for Biomedicine Wuyi University Jiangmen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[{"name":"BGI\u2010Hangzhou Hangzhou 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