title: 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.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Conley
authors.affiliation: Department of Cell Biology, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
authors.forename: Muna I
authors.initials: MI
authors.lastname: Naash
mesh_terms: D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics / Q000628:therapy*; D051379:Mice; D064531:Peripherins / Q000235:genetics*; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000628:therapy*
chemical_list: C578997:PRPH2 protein, human; D064531:Peripherins