Efficient and safe transduction of cochlear outer hair cells in adult mice with AAV2.7m8-Myo15.

Adeno-associated virus (AAV) vector-mediated inner ear gene therapy has gradually achieved successful clinical translation in individual treatment regimens. However, the low transduction efficiency of AAV vectors in the outer hair cells of adult mammals has hindered the development and application of inner ear gene therapy strategies for hearing loss. In this study, we innovatively combined the AAV2.7m8 vector with the Myo15 promoter, achieving high-efficiency transduction of the outer hair cells in adult mice across different age groups. Subsequently, we compared the results of two gene delivery methods, posterior semicircular canal injection and round window membrane injection, in adult mice. Ultimately, we successfully established a highly efficient and targeted inner ear gene delivery system by combining AAV2.7m8 with the Myo15 promoter, which effectively resolves the bottleneck of low outer hair cell transduction efficiency in adult mice. This system not only achieves high-efficiency transduction of the outer hair cells across adult mice of different ages but also demonstrates the safety of local administration, as assessed through histopathological assessments of systemic organs and inner ear tissues. This optimized delivery strategy provides a reliable technical basis for the future clinical translation of inner ear gene therapy and the development of therapeutic regimens for sensorineural hearing loss.