RHO1-2 meganuclease gene editing targets human P23H rhodopsin-induced retinitis pigmentosa to rejuvenate rods and maintain cones.

ABSTRACT: Autosomal dominant retinitis pigmentosa (adRP) is an inherited retinal dystrophy characterized by progressive vision loss and eventual blindness. The P23H mutation (proline to histidine substitution at codon 23) in the rhodopsin (RHO) gene represents the most common form of adRP in North Americans. Currently, there is no cure for P23H adRP. Genome editing targeting the mutant RHO allele, leaving a functional wildtype (WT) allele, is an attractive approach for P23H adRP, as only one copy of RHO is needed for normal retinal function. We re-engineered an I-Cre meganuclease, called RHO1-2, to target a 22bp recognition sequence encompassing the mutation responsible for the p.P23H RHO mutation. In vitro, RHO1-2, cuts human P23H RHO but not WT RHO. In vivo, we delivered scAAV5:GRK1:

SUBMITTER: Jalligampala A 

PROVIDER: S-EPMC12485717 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature