Rhodopsin P23H mutant messenger RNA (RHO P23H mRNA)

RHO P23H mutant mRNA is the messenger RNA transcript of the rhodopsin gene carrying a proline-to-histidine substitution at codon 23 (nih.gov). This mutation is the most common cause of autosomal dominant retinitis pigmentosa (adRP) in North America, accounting for approximately 10% of cases (oup.com). The mutant mRNA is translated into a misfolded rhodopsin protein that aggregates in the endoplasmic reticulum, inducing ER stress and the unfolded protein response (UPR), which ultimately leads to the death of rod photoreceptor cells (pnas.org). Therapeutic strategies targeting this mRNA, such as antisense oligonucleotides like QR-1123 (also known as ION357), aim to selectively degrade the mutant transcript while sparing the wild-type mRNA (pcori.org, fightingblindness.org). By reducing the production of the toxic mutant protein, these therapies seek to preserve retinal structure and function, potentially halting the progression of vision loss in affected patients (nih.gov). While clinical development of some candidates like QR-1123 has been suspended, the target remains a primary focus for RNA-based gene editing and silencing technologies (pcori.org, nih.gov).

Other names

RHO P23H transcriptMutant rhodopsin mRNARhodopsin P23H mRNARHO P23H variant mRNA

Selective degradation of mutant mRNA via RNase H recruitment or RNA interference to prevent translation of toxic misfolded protein.