Peripherin-2 c.623G>A mutant messenger RNA (PRPH2 c.623G>A mRNA)

Peripherin-2 (PRPH2), also known as Retinal Degeneration Slow (RDS), is a critical tetraspanin protein localized to the rims of photoreceptor outer segment discs, where it is essential for structural stability and morphogenesis (UniProt P23942). The c.623G>A mutation in the PRPH2 gene results in a p.Gly208Asp (G208D) amino acid substitution, which is a known cause of autosomal dominant retinitis pigmentosa and various pattern dystrophies (PMID: 8401583). This specific mutant mRNA serves as a therapeutic target for precision medicine approaches, such as allele-specific antisense oligonucleotides (ASOs) or RNA interference (RNAi). The goal of targeting the mutant transcript is to selectively degrade the toxic mRNA while preserving the expression of the healthy wild-type allele, thereby preventing the dominant-negative or gain-of-function effects that lead to photoreceptor cell death (PMID: 28813544). Successful modulation of this target aims to halt the progression of vision loss in patients carrying this specific genetic variant. Clinical development in this area focuses on optimizing delivery to the subretinal or intravitreal space and ensuring high specificity to avoid depleting the essential wild-type protein (PMID: 31614105).

Other names

RDS c.623G>A mRNAPRPH2 p.Gly208Asp mRNAPeripherin-2 G208D mRNATetraspanin-22 mutant mRNARetinal degeneration slow mutant mRNA

Allele-specific RNA degradation or silencing