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However, current editing therapies for genetic hearing loss have shown efficacy only in hearing rescue. In this study, we evaluated a rescue strategy using adeno-associated virus (AAV) type 2\u2013mediated delivery of\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    Cas9-sgRNA in the mature inner ear of the\n                    <jats:italic>\n                      P2rx2\n                      <jats:sup>V61L\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mouse model of autosomal dominant deafness-41 (DFNA41), a dominant, delayed-onset, and progressive hearing loss in humans. We demonstrate that local injection in adult mice results in efficient and specific editing that abolishes the mutation without notable off-target effects or AAV genome integration. Editing effectively restores long-term auditory and vestibular function. Editing further protects\n                    <jats:italic>\n                      P2rx2\n                      <jats:sup>V61L\/+<\/jats:sup>\n                    <\/jats:italic>\n                    mice from hypersensitivity to noise-induced hearing loss, a phenotype also observed in patients with DFNA41. Intervention in mice at a juvenile stage broadens the frequency range rescued, highlighting the importance of early intervention. An effective and specific gRNA for the human\n                    <jats:italic>P2RX2<\/jats:italic>\n                    V60L mutation has been identified. Our study establishes the feasibility of editing to treat DFNA41 caused by\n                    <jats:italic>P2RX2<\/jats:italic>\n                    V60L mutation in humans and opens an avenue for using editing to rescue hearing and vestibular function while mitigating noise-induced hearing loss.\n                  <\/jats:p>","DOI":"10.1172\/jci187872","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T19:53:39Z","timestamp":1760471619000},"source":"Crossref","is-referenced-by-count":8,"title":["Single-dose genome editing therapy rescues auditory and vestibular functions in adult mice with DFNA41 deafness"],"prefix":"10.1172","volume":"135","author":[{"given":"Wei","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenliang","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stewart","family":"Silver","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariel M.","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fletcher S.","family":"Robbins","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arun Prabhu","family":"Rameshbabu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head and Neck Surgery, Graduate Program in Speech and Hearing Bioscience and Technology and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA."},{"name":"Eaton-Peabody Laboratory, Massachusetts Eye and Ear, Boston, Massachusetts, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherina","family":"Walz","sequence":"additional","affiliation":[{"name":"Dr. John T. 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