Gene Therapy of Retinal Dystrophies: Achievements, Challenges and Prospects

  1. Gregory Bock Organizer,
  2. Gerry Chader Organizer and
  3. Jamie Goode
  1. Dean Bok

Published Online: 7 OCT 2008

DOI: 10.1002/0470092645.ch2

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

Bok, D. (2003) Gene Therapy of Retinal Dystrophies: Achievements, Challenges and Prospects, 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.ch2

Author Information

  1. Department of Neurobiology & Ophthalmology, Jules Stein Eye Institute and Brain Research Institute, University of California, 100 Stein Plaza, Los Angeles, CA 90095-7065, USA

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

SEARCH

Summary

Early attempts at gene therapy of inherited retinal diseases by recombinant adenovirus-vectored gene replacement in laboratory animals met with moderate success but the effect was transient. Recently, emphasis has shifted to less toxic vectors, namely recombinant adeno-associated (rAAV) viruses. Ribozymes, targeted to the P23H rhodopsin mutation in transgenic rats, significantly reduced photoreceptor loss and slowed attenuation of the electroretinogram (ERG) for 8 months. By gene replacement, rAAV-based photoreceptor rescue has been achieved in the rds−/− mouse and has restored vision in dogs carrying a RPE65 gene mutation. Minigenes for neurotrophins delivered by rAAV have been effective in achieving structural rescue of photoreceptors in rodent models of dominant disease, although this has not always been accompanied by functional rescue. One of the current challenges is the application of ribozyme therapy for dominant mutations coupled with wild-type gene augmentation to overcome haploinsufficiency. Other animal models are currently being utilized for preclinical studies as well. Spontaneously mutated Irish Setters and rd mice offer excellent subjects for the therapy of recessive mutations as do the RPE65 knockout mouse and RCS (rdy) rat. With burgeoning preclinical successes, the future looks bright for the treatment and cure of inherited retinal diseases in human patients.