Identification of Adeno-Associated Viral Vectors That Target Neonatal and Adult Mammalian Inner Ear Cell Subtypes.

Summary

Since different forms of genetic hearing loss arise from mutations in different inner ear cell types, gene therapy delivery needs vectors that can reliably reach those specific cells. This study systematically screened 12 AAV serotypes (AAV1, 2, 5, 6, 6.2, 7, 8, 9, rh.8, rh.10, rh.39, rh.43) carrying a GFP reporter in neonatal and adult mouse inner ears. Most serotypes infected both ages with varying specificity and efficiency, most consistently reaching the cochlear sensory epithelium (hair cells and supporting cells), giving the field a working map of which AAV vectors to use for which target cell type.

Key findings

• 12 AAV serotypes were screened by microinjection into neonatal and adult mouse inner ears.
• The cochlear sensory epithelium (hair cells and supporting cells) was the most consistently targeted region across serotypes.
• Neonatal inner ear delivery did not adversely affect hearing; in adults, the injection procedure itself could damage outer hair cells.
• Transgene expression was sustained and most infected cells survived, supporting AAV as a viable long-term gene delivery platform for the inner ear.