A dual-AAV approach restores fast exocytosis and partially rescues auditory function in deaf otoferlin knock-out mice.

ABSTRACT: Normal hearing and synaptic transmission at afferent auditory inner hair cell (IHC) synapses require otoferlin. Deafness DFNB9, caused by mutations in the OTOF gene encoding otoferlin, might be treated by transferring wild-type otoferlin cDNA into IHCs, which is difficult due to the large size of this transgene. In this study, we generated two adeno-associated viruses (AAVs), each containing half of the otoferlin cDNA Co-injecting these dual-AAV2/6 half-vectors into the cochleae of 6- to 7-day-old otoferlin knock-out (Otof^-/-) mice led to the expression of full-length otoferlin in up to 50% of IHCs. In the cochlea, otoferlin was selectively expressed in auditory hair cells. Dual-AAV transduction of Otof^-/- IHCs fully restored fast exocytosis, whil

SUBMITTER: Al-Moyed H 

PROVIDER: S-EPMC6328916 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature