Exogenous Photoreceptor-Specific N-Glycosylated PROM1 Rescues Retinal Degeneration in Patient and Mouse Models - PubMed
6 hours ago
- #gene therapy
- #PROM1
- #retinal dystrophy
- PROM1-associated inherited retinal dystrophy (PROM1-IRD) is caused by pathogenic variants of PROM1, leading to retina-specific disorders.
- PROM1 shows photoreceptor-enriched mRNA splicing isoforms and distinct N-glycosylation patterns during photoreceptor differentiation.
- Patient-derived models with PROM1 c.619G>T mutation showed complete loss of PROM1 protein and disrupted outer segment (OS)-like structures.
- A photoreceptor-targeted AAV7m8-CRXp-hPROM1 vector restored PROM1 expression and rescued OS-like structures in patient-derived retinal organoids.
- Subretinal delivery of AAV8-CRXp-hPROM1 in Prom1-/- mice preserved OS morphology and improved visual function, supporting gene therapy for PROM1-IRD.