Rhodopsin (P23H mutant) messenger RNA (RHO-P23H mRNA) (RHO-P23H mRNA)

P23H mutant rhodopsin mRNA is the messenger RNA transcript of the RHO gene containing a specific point mutation (c.68C>A) that results in a proline-to-histidine substitution at position 23 of the rhodopsin protein. This mutation is the most prevalent cause of autosomal dominant retinitis pigmentosa (adRP) in North America, accounting for approximately 10% of cases (Source: NIH, PubMed). The presence of this mutant mRNA leads to the production of a misfolded protein that accumulates in the endoplasmic reticulum, triggering the unfolded protein response and eventual apoptosis of rod photoreceptor cells (Source: UniProt). Therapeutic approaches targeting this mRNA focus on allele-specific silencing to selectively degrade the mutant transcript while preserving the wild-type mRNA necessary for vision. Antisense oligonucleotides (ASOs), such as QR-1123 (Ultevursen), are designed to bind to the mutant sequence and induce RNase H-mediated degradation (Source: ProQR Therapeutics). Successful targeting of this mRNA aims to reduce the proteotoxic stress in the retina and slow the progression of vision loss in affected patients.

Other names

P23H RHO mRNAMutant rhodopsin transcriptRHO P23H mRNAPro23His rhodopsin mRNARhodopsin P23H mutant transcript

Allele-specific knockdown of mutant mRNA via RNase H-mediated degradation or RNA interference (RNAi) to prevent the translation of misfolded rhodopsin protein.