UCLA

Usher Syndrome 1B (USH1B) is a severe genetic disorder characterized by congenital deafness and progressive vision loss due to retinitis pigmentosa. The role of myosin VIIa in the retinal pigment epithelium (RPE) is critical for photoreceptor function and survival, and mutations in the myosin VIIa gene (MYO7A) are the primary cause of USH1B. This work aims to advance therapeutic tools for USH1B and introduce tools that shed light on the functional roles of myosin VIIa within the RPE. We employed novel gene editing tools to correct Myo7a mutations using an engineered cell line. This cell line can be used as a cost-effective high-throughput approach for screening guide RNA sequences for producing precise gene edits. Additionally, we developed and optimized gene vectors for efficient delivery of the base editing system to disease models. This work focused on restoring functional myosin VIIa protein expression in the shaker-1 mouse, an animal model of USH1B. Our results highlight the promise of base editing for advancing approaches in gene therapy, and introduce a novel set of tools for better exploring the biological roles of myosin VIIa.