Restoration of Hearing in the VGLUT3 Knockout Mouse Using Virally Mediated Gene Therapy

摘要

Mice lacking the vesicular glutamate transporter-3 (VGLUT3) are congenitally deaf due to loss of glutamate release at the inner hair cell afferent synapse. Cochlear delivery of VGLUT3 using adeno-associated virus type 1 (AAV1) leads to transgene expression in only inner hair cells (IHCs), despite broader viral uptake. Within 2 weeks of AAV1-VGLUT3 delivery, auditory brainstem response (ABR) thresholds normalize, along with partial rescue of the startle response. Lastly, we demonstrate partial reversal of the morphologic changes seen within the afferent IHC ribbon synapse. These findings represent a successful restoration of hearing by gene replacement in mice, which is a significant advance toward gene therapy of human deafness. In a mouse model of genetic deafness, Akil et al. use viral-driven gene therapy to restore hearing. The successful restoration of hearing by gene replacement in this animal model represents an important step toward gene therapy for human deafness.