A comprehensive review of retinal gene therapy

Mol Ther. 2013 Mar;21(3):509-19. doi: 10.1038/mt.2012.280. Epub 2013 Jan 29.

Abstract

Blindness, although not life threatening, is a debilitating disorder for which few, if any treatments exist. Ocular gene therapies have the potential to profoundly improve the quality of life in patients with inherited retinal disease. As such, tremendous focus has been given to develop such therapies. Several factors make the eye an ideal organ for gene-replacement therapy including its accessibility, immune privilege, small size, compartmentalization, and the existence of a contralateral control. This review will provide a comprehensive summary of (i) existing gene therapy clinical trials for several genetic forms of blindness and (ii) preclinical efficacy and safety studies in a variety of animal models of retinal disease which demonstrate strong potential for clinical application. To be as comprehensive as possible, we include additional proof of concept studies using gene replacement, neurotrophic/neuroprotective, optogenetic, antiangiogenic, or antioxidative stress strategies as well as a description of the current challenges and future directions in the ocular gene therapy field to this review as a supplement.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • ATP-Binding Cassette Transporters / genetics
  • Animals
  • Clinical Trials as Topic
  • Dependovirus
  • Disease Models, Animal
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Guanylate Cyclase / genetics
  • Humans
  • Proto-Oncogene Proteins / genetics
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptors, Cell Surface / genetics
  • Retina / pathology*
  • Retinal Diseases / genetics*
  • Retinal Diseases / therapy*
  • c-Mer Tyrosine Kinase
  • cis-trans-Isomerases / genetics

Substances

  • ABCA4 protein, human
  • ATP-Binding Cassette Transporters
  • Proto-Oncogene Proteins
  • Receptors, Cell Surface
  • guanylate cyclase 1
  • MERTK protein, human
  • Receptor Protein-Tyrosine Kinases
  • c-Mer Tyrosine Kinase
  • retinoid isomerohydrolase
  • Guanylate Cyclase
  • cis-trans-Isomerases