In vivo prime editing rescues photoreceptor degeneration in nonsense mutant retinitis pigmentosa.

ABSTRACT: The next-generation gene editing tool, prime editing (PE), is adept at correcting point mutations precisely with high editing efficiency and rare off-target events and shows promising therapeutic value in treating hereditary diseases. Retinitis pigmentosa (RP) is the most common type of inherited retinal dystrophy and is characterized by progressive degeneration of retinal photoreceptors and, consequently, visual decline. To date, effective treatments for RP are lacking. Herein, a PE system is designed to target the PDE6B Y347X mutation in the rd1 mouse strain, a preclinical RP model. We screen and develop the PE system with epegRNA and RT^ΔRnH, which is delivered via dual-AAV in vivo with an editing efficiency of 26.47 ± 13.35%, with negligible off-target effects confirmed by AI

SUBMITTER: Fu Y 

PROVIDER: S-EPMC11893901 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature