CRISPR genome surgery in a novel humanized model for autosomal dominant retinitis pigmentosa.

ABSTRACT: Mutations in rhodopsin (RHO) are the most common causes of autosomal dominant retinitis pigmentosa (adRP), accounting for 20% to 30% of all cases worldwide. However, the high degree of genetic heterogeneity makes development of effective therapies cumbersome. To provide a universal solution to RHO-related adRP, we devised a CRISPR-based, mutation-independent gene ablation and replacement (AR) compound therapy carried by a dual AAV2/8 system. Moreover, we developed a novel hRHO^C110R/hRHO^WT humanized mouse model to assess the AR treatment in vivo. Results show that this humanized RHO mouse model exhibits progressive rod-cone degeneration that phenocopies hRHO^C110R/hRHO^WT patients. In vivo transduction of AR AAV8 dual vectors remarkably ablates endo

SUBMITTER: Wu WH 

PROVIDER: S-EPMC9077379 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature