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There are reports on\n                    <jats:italic>Otof<\/jats:italic>\n                    \u2010related gene therapy in mice, but there is no preclinical research on the drug evaluations. Here, Anc80L65 and the mouse hair cell\u2010specific Myo15 promoter (mMyo15) are used to selectively and effectively deliver human\n                    <jats:italic>OTOF<\/jats:italic>\n                    to hair cells in mice and nonhuman primates to evaluate the efficacy and safety of\n                    <jats:italic>OTOF<\/jats:italic>\n                    gene therapy drugs. A new dual\u2010AAV\n                    <jats:italic>\u2010OTOF\u2010<\/jats:italic>\n                    hybrid strategy to transfer full\u2010length\n                    <jats:italic>OTOF<\/jats:italic>\n                    is generated, which can stably restore hearing in adult OTOF\n                    <jats:sup>p.Q939*\/Q939*<\/jats:sup>\n                    mice with profound deafness, with the longest duration being at least 150 days, and the best therapeutic effect without difference in hearing from wild\u2010type mice. An AAV microinjection method into the cochlea of cynomolgus monkeys without hearing impairment is further established and found the\n                    <jats:italic>OTOF<\/jats:italic>\n                    can be safely and effectively driven by the mMyo15 promoter in hair cells. In addition, the therapeutic dose of AAV drugs has no impact on normal hearing and does not cause significant systemic toxicity both in mouse and nonhuman primates. In summary, this study develops a potential gene therapy strategy for DFNB9 patients in the clinic and provides complete, standardized, and systematic research data for clinical research and application.\n                  <\/jats:p>","DOI":"10.1002\/advs.202306201","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T08:25:39Z","timestamp":1701159939000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":70,"title":["Preclinical Efficacy And Safety Evaluation of AAV\u2010\n                    <i>OTOF<\/i>\n                    in DFNB9 Mouse Model And Nonhuman Primate"],"prefix":"10.1002","volume":"11","author":[{"given":"Jieyu","family":"Qi","sequence":"first","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck Surgery Zhongda Hospital School of Life Sciences and Technology School of Medicine Advanced Institute for Life and Health Jiangsu Province High\u2010Tech Key Laboratory for Bio\u2010Medical Research Southeast University  Nanjing 210096 China"},{"name":"Co\u2010Innovation Center of Neuroregeneration Nantong University  Nantong 226001 China"},{"name":"School of Life Science Beijing Institute of Technology  Beijing 100081 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liyan","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck Surgery Zhongda Hospital School of Life Sciences and Technology School of Medicine Advanced Institute for Life and Health Jiangsu Province High\u2010Tech Key Laboratory for Bio\u2010Medical Research Southeast University  Nanjing 210096 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangzhi","family":"Tan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck Surgery Zhongda Hospital School of Life Sciences and Technology School of Medicine Advanced Institute for Life and Health Jiangsu Province High\u2010Tech Key Laboratory for Bio\u2010Medical Research Southeast University  Nanjing 210096 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology Affiliated Drum Tower Hospital of Nanjing University Medical School  Nanjing 210008 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinyi","family":"Zhou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck Surgery Zhongda Hospital School of Life Sciences and Technology School of Medicine Advanced Institute for Life and Health Jiangsu Province High\u2010Tech Key Laboratory for Bio\u2010Medical Research Southeast University  Nanjing 210096 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Digital Medical Engineering Department of Otolaryngology Head and Neck Surgery Zhongda Hospital School of Life Sciences and Technology School of Medicine Advanced Institute for Life and Health Jiangsu Province High\u2010Tech Key Laboratory for Bio\u2010Medical Research Southeast University  Nanjing 210096 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Senior Department of Otolaryngology\u2010Head &amp; Neck Surgery the Sixth Medical Center of Chinese PLA General Hospital  Beijing 100048 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chaorong","family":"Yu","sequence":"additional","affiliation":[{"name":"Otovia Therapeutics Inc.  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