Gene therapy for PRPH2-associated ocular disease: challenges and prospects.

Abstract

The peripherin-2 (PRPH2) gene encodes a photoreceptor-specific tetraspanin protein called peripherin-2/retinal degeneration slow (RDS), which is critical for the formation and maintenance of rod and cone outer segments. Over 90 different disease-causing mutations in PRPH2 have been identified, which cause a variety of forms of retinitis pigmentosa and macular degeneration. Given the disease burden associated with PRPH2 mutations, the gene has long been a focus for preclinical gene therapy studies. Adeno-associated viruses and compacted DNA nanoparticles carrying PRPH2 have been successfully used to mediate improvement in the rds(-/-) and rds(+/-) mouse models. However, complexities in the pathogenic mechanism for PRPH2-associated macular disease coupled with the need for a precise dose of peripherin-2 to combat a severe haploinsufficiency phenotype have delayed the development of clinically viable genetic treatments. Here we discuss the progress and prospects for PRPH2-associated gene therapy.

• Authors: Shannon M Conley, Muna I Naash
• Journal: Cold Spring Harbor perspectives in medicine (Cold Spring Harb Perspect Med) Vol. 4 Issue 11 Pg. a017376 (Aug 28 2014) ISSN: 2157-1422 [Electronic] United States
• PMID: 25167981 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Review)
• Copyright: Copyright © 2014 Cold Spring Harbor Laboratory Press; all rights reserved.

Chemical References

• PRPH2 protein, human
• Peripherins

Topics

• Animals
• Genetic Therapy (methods)
• Humans
• Macular Degeneration (genetics, therapy)
• Mice
• Peripherins (genetics)
• Retinitis Pigmentosa (genetics, therapy)