Functional, sustained recovery of hearing in Otoferlin-deficient mice using DB-OTO, a hair-cell-specific AAV-based gene therapy.

ABSTRACT: Biallelic loss-of-function variants in the Otoferlin gene (OTOF) lead to congenital hearing loss in both humans and mice. We developed DB-OTO, a hair-cell-specific adeno-associated virus (AAV)-based dual-vector gene therapy designed to restore hearing in individuals with OTOF-related hearing loss. DB-OTO is composed of two AAV1 vectors that reconstitute a functional OTOF gene expression cassette to form the full-length human OTOF variant 5 (h OTOFv5). A synthetic promoter (mMyo15) based on the murine Myosin 15 a gene was engineered to restrict the transgene expression to hair cells. The promoter construct was chosen after comparison of multiple variants using a GFP reporter in ex vivo murine explant models, follow

SUBMITTER: Chung Y 

PROVIDER: S-EPMC12481892 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature