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Effective therapies for\n                    <jats:italic>ATP6V1B2<\/jats:italic>\n                    \u2010associated hearing loss remain elusive. The study generates a hair cell\u2010specific knockout mouse (\n                    <jats:italic>\n                      Atp6v1b2\n                      <jats:sup>fl\/fl<\/jats:sup>\n                    <\/jats:italic>\n                    ;\n                    <jats:italic>\n                      Atoh1\n                      <jats:sup>Cre\/+<\/jats:sup>\n                    <\/jats:italic>\n                    ) recapitulating the human phenotypes, with pathological features including hair cell loss and abnormal lysosomal morphology and function. To enhance therapeutic precision and minimize toxicity, an optimized adeno\u2010associated virus\u2010inner ear vector incorporating promoter enhancer 3 (AAV\u2010ie\u2010Eh3) is engineered. A single administration of AAV\u2010ie\u2010Eh3\u2010m\n                    <jats:italic>Atp6v1b2<\/jats:italic>\n                    into the scala media at postnatal days 0\u20132, prevented hair cell degeneration, restored lysosome morphology, and robustly rescued auditory and vestibular function for at least 24 weeks. The findings highlight the critical role of\n                    <jats:italic>Atp6v1b2<\/jats:italic>\n                    in lysosomal function and demonstrate AAV\u2010ie\u2010Eh3 as a potent gene delivery tool for inner ear therapy. This study establishes a novel therapeutic paradigm for\n                    <jats:italic>ATP6V1B2\u2010<\/jats:italic>\n                    associated hearing loss and vestibular dysfunction, with significant clinical potential.\n                  <\/jats:p>","DOI":"10.1002\/advs.202408878","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T16:02:55Z","timestamp":1741708975000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Single Administration of AAV\u2010m\n                    <i>Atp6v1b2<\/i>\n                    Gene Therapy Rescues Hearing and Vestibular Disorders Caused by\n                    <i>Atp6v1b2<\/i>\n                    \u2010Induced Lysosomal Dysfunction in Hair Cells"],"prefix":"10.1002","volume":"12","author":[{"given":"Gege","family":"Wei","sequence":"first","affiliation":[{"name":"Senior Department of Otolaryngology Head and Neck Surgery the 6th Medical Center of Chinese PLA General Hospital Chinese PLA Medical School  Beijing 100853 China"},{"name":"State Key Laboratory of Hearing and Balance Science  Beijing 100853 China"},{"name":"National Clinical Research Center for Otolaryngologic Diseases  Beijing 100853 China"},{"name":"Key Laboratory of Hearing Science Ministry of Education  Beijing 100853 China"},{"name":"Beijing Key Laboratory of Hearing Impairment Prevention and Treatment  Beijing 100853 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiwei","family":"Qiu","sequence":"additional","affiliation":[{"name":"Chinese Institute for Brain Research  Beijing 102206 China"},{"name":"School of Life Sciences Tsinghua University  Beijing 100084 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology PLA Rocket Force Characteristic Medical Center  16# XinWai Da Jie Beijing 100088 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