Mutation-independent gene knock-in therapy targeting 5′UTR for autosomal dominant retinitis pigmentosa
Duc Anh Hoang, Baoshan Liao, Zongli Zheng, Wenjun Xiong
Abstract
Retinitis pigmentosa (RP) is an inherited photoreceptor degeneration disease with high genetic heterogeneity (>90 disease-causing genes according to RetNet: https://web.sph.uth.edu/RetNet/sum-dis.htm ). Taking a single RP disease gene RHO as an example, there are more than two hundred loss-of-function and gain-of-function mutations identified. 1 While gene supplementation therapy has emerged as the most promising treatment for autosomal recessive RP (arRP) and X-linked RP (ClinicalTrials identifier: NCT01482195, NCT03328130, NCT03116113, NCT03252847, NCT03316560), therapeutic approaches to treat autosomal dominant RP (adRP) fall behind due to the low efficiency to disrupt mutant alleles specifically and a broad spectrum of the gain-of-function mutations.