ShH10 viral vector for safe, efficient, and selective transduction of inner ear supporting cells

Abstract

Hearing loss is the most prevalent type of sensory deficit in humans. Recent studies have found adeno-associated viruses (AAVs) targeting hair cells as promising vectors for inner ear gene therapy. However, targeting non-sensory cell types, which are often affected by genetic mutations causing sensorineural hearing loss, remains a challenge. In this study, we characterize the serotype ShH10, an AAV variant we show to have high tropism for supporting cells in the mouse cochlea and utricle. We demonstrate that ShH10 efficiently targets all subtypes of supporting cells along the length of cochlear duct without negatively impacting auditory function. Unlike many other potent AAV vectors tested in the inner ear, ShH10 does not spread to the central nervous system or the contralateral ear, allowing for more targeted therapy. Future studies in disease models and larger animal models will be crucial for validating the clinical potential of this serotype in correcting both genetic and acquired hearing dysfunction.