Gene therapy for inherited retinal and optic nerve degenerations

Expert Opin Biol Ther. 2018 Jan;18(1):37-49. doi: 10.1080/14712598.2018.1389886. Epub 2017 Oct 23.


Introduction: The eye is a target for investigational gene therapy due to the monogenic nature of many inherited retinal and optic nerve degenerations (IRD), its accessibility, tight blood-ocular barrier, the ability to non-invasively monitor for functional and anatomic outcomes, as well as its relative immune privileged state.Vectors currently used in IRD clinical trials include adeno-associated virus (AAV), small single-stranded DNA viruses, and lentivirus, RNA viruses of the retrovirus family. Both can transduce non-dividing cells, but AAV are non-integrating, while lentivirus integrate into the host cell genome, and have a larger transgene capacity.

Areas covered: This review covers Leber's congenital amaurosis, choroideremia, retinitis pigmentosa, Usher syndrome, Stargardt disease, Leber's hereditary optic neuropathy, Achromatopsia, and X-linked retinoschisis.

Expert opinion: Despite great potential, gene therapy for IRD raises many questions, including the potential for less invasive intravitreal versus subretinal delivery, efficacy, safety, and longevity of response, as well as acceptance of novel study endpoints by regulatory bodies, patients, clinicians, and payers. Also, ultimate adoption of gene therapy for IRD will require widespread genetic screening to identify and diagnose patients based on genotype instead of phenotype.

Keywords: Gene therapy; Leber’s Congenital Amaurosis; Stargardt Disease; adeno-associated virus; choroideremia; inherited retinal disease; retinitis pigmentosa.

Publication types

  • Review

MeSH terms

  • Choroideremia / pathology
  • Choroideremia / therapy
  • Clinical Trials as Topic
  • Color Vision Defects / pathology
  • Color Vision Defects / therapy
  • Dependovirus / genetics
  • Genetic Therapy*
  • Genetic Vectors / genetics
  • Genetic Vectors / metabolism
  • Humans
  • Lentivirus / genetics
  • Macular Degeneration / congenital
  • Macular Degeneration / pathology
  • Macular Degeneration / therapy
  • Nerve Degeneration / pathology
  • Nerve Degeneration / therapy*
  • Stargardt Disease
  • Usher Syndromes / pathology
  • Usher Syndromes / therapy
  • cis-trans-Isomerases / genetics


  • retinoid isomerohydrolase
  • cis-trans-Isomerases

Supplementary concepts

  • Stargardt disease 1