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Cell tropism of adeno-associated viruses within the mouse inner ear in vivo: from embryonic to adult stages
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Cell tropism of adeno-associated viruses within the mouse inner ear in vivo: from embryonic to adult stages
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Cell tropism of adeno-associated viruses within the mouse inner ear in vivo: from embryonic to adult stages
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Journal Article
Cell tropism of adeno-associated viruses within the mouse inner ear in vivo: from embryonic to adult stages
2025
Overview
Adeno-associated virus (AAV)-based gene therapy is emerging as a promising treatment for deafness and vestibular deficits, due to the variety of available serotypes that offer a large range of cell targeting capabilities. Nevertheless, the tropism of these AAV serotypes for sensory inner ear cells varies greatly as the cochlea matures, presenting a significant burden for successful preclinical trials. Therefore, identifying serotypes with strong tropism for cochlear and vestibular hair cells during key stages of development in mouse inner ear, the most widely used preclinical model, is essential for advancing clinical applications. We conducted a comparative analysis of the cellular tropism and hair-cell transduction rates of four AAV serotypes in the cochlea and vestibular organs during maturation. We used AAV2, AAV8, AAV9-PHP.eB, and Anc80L65 at the embryonic, neonatal, and adult stages. Our results indicate that the cell transduction rate of these four serotypes varies with age. Notably outer hair cells were mostly targeted during the embryonic stage, inner hair cells were primarily transduced principally at the mature stage, and vestibular hair cells were the most permissive at the neonatal stage. These results provide new insights for preclinical gene therapy studies for the inner ear with potential implications for therapeutic outcomes.
