The new landscape of retinal gene therapy

Am J Med Genet C Semin Med Genet. 2020 Sep;184(3):846-859. doi: 10.1002/ajmg.c.31842. Epub 2020 Sep 5.

Abstract

Novel therapeutics for inherited retinal dystrophies (IRDs) have rapidly evolved since groundbreaking clinical trials for LCA due to RPE65 mutations led to the first FDA-approved in vivo gene therapy. Since then, advancements in viral vectors have led to more efficient AAV transduction and developed other viral vectors for gene augmentation therapy of large gene targets. Furthermore, significant developments in gene editing and RNA modulation technologies have introduced novel capabilities for treatment of autosomal dominant diseases, intronic mutations, and/or large genes otherwise unable to be treated with current viral vectors. We highlight strategies currently being evaluated in gene therapy clinical trials and promising preclinical developments for IRDs.

Keywords: RNA modulation; gene editing; gene therapy; inherited retinal dystrophies.

Publication types

  • Review

MeSH terms

  • Gene Editing*
  • Genetic Therapy*
  • Genetic Vectors / genetics
  • Genetic Vectors / therapeutic use
  • Humans
  • Mutation / genetics
  • Retinal Dystrophies / genetics
  • Retinal Dystrophies / pathology
  • Retinal Dystrophies / therapy*
  • cis-trans-Isomerases / genetics*
  • cis-trans-Isomerases / therapeutic use

Substances

  • retinoid isomerohydrolase
  • cis-trans-Isomerases