Preclinical evaluation of the efficacy and safety of AAV1-hOTOF in mice and nonhuman primates.

ABSTRACT: Pathogenic mutations in the OTOF gene cause autosomal recessive hearing loss (DFNB9), one of the most common forms of auditory neuropathy. There is no biological treatment for DFNB9. Here, we designed an OTOF gene therapy agent by dual-adeno-associated virus 1 (AAV1) carrying human OTOF coding sequences with the expression driven by the hair cell-specific promoter Myo15, AAV1-hOTOF. To develop a clinical application of AAV1-hOTOF gene therapy, we evaluated its efficacy and safety in animal models using pharmacodynamics, behavior, and histopathology. AAV1-hOTOF inner ear delivery significantly improved hearing in Otof^-/- mice without affecting normal hearing in wild-type mice. AAV1 was predominately distributed to the cochlea, although it was de

SUBMITTER: Zhang L 

PROVIDER: S-EPMC10679773 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature