Prospects for Gene Therapy

  1. Gregory Bock Organizer,
  2. Gerry Chader Organizer and
  3. Jamie Goode
  1. Robin R. Ali

Published Online: 7 OCT 2008

DOI: 10.1002/0470092645.ch12

Retinal Dystrophies: Functional Genomics to Gene Therapy: Novartis Foundation Symposium 255

Retinal Dystrophies: Functional Genomics to Gene Therapy: Novartis Foundation Symposium 255

How to Cite

Ali, R. R. (2003) Prospects for Gene Therapy, in Retinal Dystrophies: Functional Genomics to Gene Therapy: Novartis Foundation Symposium 255 (eds G. Bock, G. Chader and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/0470092645.ch12

Author Information

  1. Molecular Genetics, Institute of Ophthalmology, University College London, Bath St, London EC1V 9EL, UK

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 9 DEC 2003

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470853573

Online ISBN: 9780470092644



Inherited retinal disease, which includes conditions such as retinitis pigmentosa (RP), affects about 1/3000 of the population in the Western world. It is characterized by gradual loss of vision and results from mutations in any one of 60 or so different genes. There are currently no effective treatments, but many of the genes have now been identified and their functions elucidated, providing a major impetus to develop gene-based treatments. Many of the disease genes are photoreceptor- or retinal pigment epithelium (RPE) cell specific. Since adeno-associated viral (AAV) vectors can be used for efficient gene transfer to these two cell types, we are developing AAV-mediated gene therapy approaches for inherited retinal degeneration using animal models that have defects in these cells. The retinal degeneration slow (rds or Prph2Rd2/Rd2) mouse, a model of recessive RP, lacks a functional gene encoding peripherin 2, which is a photoreceptor-specific protein required for the formation of outer segment discs. We have previously demonstrated restoration of photoreceptor ultrastructure and function by AAV-mediated gene transfer of peripherin 2. We have now extended our assessment to central visual neuronal responses in order to show an improvement of central visual function. The Royal College of Surgeons (RCS) rat, provides another model of recessive RP. Here the defect is due to a defect in Mertk, a gene that is expressed in the RPE and encodes a receptor tyrosine kinase that is thought to be involved in the recognition and binding of outer segment debris. The gene defect results in the inability of the RPE to phagocytose the shed outer segments from photoreceptor cells. The resulting accumulation of debris between the RPE and the neuroretina leads to progressive loss of photoreceptor cells. AAV-mediated delivery of Mertk to the RPE results in reduction of debris indicating that the phagocytosing function of the RPE is restored and delays the degeneration of the photoreceptor cells 3–4 months. Our results, along with those of other groups support the use of AAV vectors for the treatment of inherited retinal degeneration.