RNA base editing therapy cures hearing loss induced by OTOF gene mutation.

ABSTRACT: Otoferlin (OTOF) gene mutations represent the primary cause of hearing impairment and deafness in auditory neuropathy. The c.2485C>T (p. Q829X) mutation variant is responsible for approximately 3% of recessive prelingual deafness cases within the Spanish population. Previous studies have used two recombinant AAV vectors to overexpress OTOF, albeit with limited efficacy. In this study, we introduce an enhanced mini-dCas13X RNA base editor (emxABE) delivered via an AAV9 variant, achieving nearly 100% transfection efficiency in inner hair cells. This approach is aimed at treating OTOF^Q829X, resulting in an approximately 80% adenosine-to-inosine conversion efficiency in humanized Otof^Q829X/Q829X mice. Following a single scala media injection of emxABE targeting OTOF^Q

SUBMITTER: Xue Y 

PROVIDER: S-EPMC10727966 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature