PCDH15 dual-AAV gene therapy for deafness and blindness in Usher syndrome type 1F models.

ABSTRACT: Usher syndrome type 1F (USH1F), resulting from mutations in the protocadherin-15 (PCDH15) gene, is characterized by congenital lack of hearing and balance, and progressive blindness in the form of retinitis pigmentosa. In this study, we explore an approach for USH1F gene therapy, exceeding the single AAV packaging limit by employing a dual-adeno-associated virus (dual-AAV) strategy to deliver the full-length PCDH15 coding sequence. We demonstrate the efficacy of this strategy in mouse USH1F models, effectively restoring hearing and balance in these mice. Importantly, our approach also proves successful in expressing PCDH15 protein in clinically relevant retinal models, including human retinal organoids and nonhuman primate retina, showing efficient targeting of photoreceptors and proper pr

SUBMITTER: Ivanchenko MV 

PROVIDER: S-EPMC11601915 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature