Project Details

In vivo prime editing to rescue autosomal dominant retinitis pigmentosa in pediatric animal models

Paul Chen, PhD

Summary

BACKGROUND: Retinitis pigmentosa is a primary genetic cause of retinal degeneration and vision loss in children, for which the p.Pro23His (c.68C>A) mutation in the rhodopsin gene (RHO) is the most prevalent autosomal dominant cause. GAP: There is no efficacious, approved treatment for RHO-P23H retinitis pigmentosa. No prior research efforts have directly corrected the root cause of disease, the disease-causing p.Pro23His (c.68C>A) mutation in RHO. HYPOTHESIS: Prime editing-based correction of the p.Pro23His (c.68C>A) mutation in RHO—that is, reversion of the disease-causing mutation back to wildtype—in rod photoreceptor cells in vivo will mitigate rod damage, retinal deterioration, and vision loss in a pediatric animal model of RHO-P23H retinitis pigmentosa. METHODS: We will develop an efficient prime editing system to correct the RHO-P23H (c.68C>A) mutation in human cell lines, characterizing both on-target and off-target editing. We will then study genotypic and phenotypic treatment effects of single-injection in vivo prime editing correction of RHO-P23H in a pediatric animal model. RESULTS: Pending. IMPACT: If successful, this work potentiates a one-time treatment for the most prevalent dominantly inherited retinopathy affecting children, RHO-P23H RP. Website Link: https://www.liugroup.us/