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The efficacy of adeno\u2010associated virus (AAV)\u2010mediated\n                    <jats:italic>OTOF<\/jats:italic>\n                    gene replacement therapy is extensively validated in\n                    <jats:italic>Otof<\/jats:italic>\n                    \u2010deficient mice. However, the clinical safety and efficacy of AAV\u2010\n                    <jats:italic>OTOF<\/jats:italic>\n                    is not reported. Here, AAV\u2010\n                    <jats:italic>OTOF<\/jats:italic>\n                    is generated using good manufacturing practice and validated its efficacy and safety in mouse and non\u2010human primates in order to determine the optimal injection dose, volume, and administration route for clinical trials. Subsequently, AAV\u2010\n                    <jats:italic>OTOF<\/jats:italic>\n                    is delivered into one cochlea of a 5\u2010year\u2010old deaf patient and into the bilateral cochleae of an 8\u2010year\u2010old deaf patient with\n                    <jats:italic>OTOF<\/jats:italic>\n                    mutations. Obvious hearing improvement is detected by the auditory brainstem response (ABR) and the pure\u2010tone audiometry (PTA) in these two patients. Hearing in the injected ear of the 5\u2010year\u2010old patient can be restored to the normal range at 1 month after AAV\u2010\n                    <jats:italic>OTOF<\/jats:italic>\n                    injection, while the 8\u2010year\u2010old patient can hear the conversational sounds. Most importantly, the 5\u2010year\u2010old patient can hear and recognize speech only through the AAV\u2010\n                    <jats:italic>OTOF<\/jats:italic>\n                    \u2010injected ear. This study is the first to demonstrate the safety and efficacy of AAV\u2010\n                    <jats:italic>OTOF<\/jats:italic>\n                    in patients, expands and optimizes current\n                    <jats:italic>OTOF<\/jats:italic>\n                    \u2010related gene therapy and provides valuable information for further application of gene therapies for deafness.\n                  <\/jats:p>","DOI":"10.1002\/advs.202306788","type":"journal-article","created":{"date-parts":[[2024,1,8]],"date-time":"2024-01-08T09:31:12Z","timestamp":1704706272000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":173,"title":["AAV\u2010Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness"],"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":"Department of Neurology, Aerospace Center Hospital, School of Life Science Beijing Institute of Technology  Beijing 100081 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 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