Antisense oligonucleotide therapy for proline-23-histidine autosomal dominant retinitis pigmentosa

Curr Opin Ophthalmol. 2023 May 1;34(3):226-231. doi: 10.1097/ICU.0000000000000947. Epub 2023 Mar 14.

Abstract

Purpose of review: To discuss antisense oligonucleotide (ASON) therapy for autosomal dominant retinitis pigmentosa (adRP) caused by the proline-23-histidine (P23H) mutation in the rhodopsin gene.

Recent findings: Viral and nonviral therapies to treat adRP are currently under investigation. A promising therapeutic option is a nonviral approach using ASONs. This form of genetic therapy has demonstrated a dose-dependent and highly selective reduction of P23H mutant rhodopsin mRNA in animal models, and it is currently being investigated as a human phase 1/2 clinical trial.

Summary: There are promising new therapies to treat adRP. ASON has shown encouraging results in animal models and has undergone a phase 1 clinical trial. ASON does not use a viral vector, is delivered with standard intravitreal injection, and its effects are reversible.

Publication types

  • Review

MeSH terms

  • Animals
  • Histidine / genetics
  • Humans
  • Mutation
  • Oligonucleotides, Antisense / therapeutic use
  • Proline / genetics
  • Retinitis Pigmentosa* / drug therapy
  • Retinitis Pigmentosa* / genetics
  • Rhodopsin* / genetics

Substances

  • Rhodopsin
  • Histidine
  • Proline
  • Oligonucleotides, Antisense