title: Gene Therapy of ABCA4-Associated Diseases.
abstract: The ATP-binding cassette (ABC) transporter gene, ABCA4 (ABCR), was characterized in 1997 as the causal gene for autosomal recessive Stargardt disease (STGD1). Shortly thereafter several other phenotypes were associated with mutations in ABCA4, which now have collectively emerged as the most frequent cause of retinal degeneration phenotypes of Mendelian inheritance. ABCA4 functions as an important transporter (or "flippase") of vitamin A derivatives in the visual cycle. Several ways to alleviate the effects of the defective ABCA4 protein, which cause accumulation of 11-cis and all-trans-retinal in photoreceptors and lipofuscin in the retinal pigment epithelium, have been proposed. Although ABCA4 has proven to be a difficult research target, substantial progress through genetic, functional, and translational studies has allowed major advances in therapeutic applications for ABCA4-associated pathology, which should be available to patients in the (near) future. Here, we summarize the status of the gene therapy-based treatment options of ABCA4-associated diseases.
authors.affiliation: Telethon Institute of Genetics and Medicine, Naples, 80131 Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Auricchio
authors.affiliation: Telethon Institute of Genetics and Medicine, Naples, 80131 Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Trapani
authors.affiliation: Department of Ophthalmology, and Department of Pathology and Cell Biology, Columbia University, New York, New York 10032.
authors.forename: Rando
authors.initials: R
authors.lastname: Allikmets
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000818:Animals; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008268:Macular Degeneration / Q000151:congenital* / Q000628:therapy; D051379:Mice; D009154:Mutation; D010641:Phenotype; D012162:Retinal Degeneration / Q000628:therapy*; D000080362:Stargardt Disease
chemical_list: C056475:ABCA4 protein, human; D018528:ATP-Binding Cassette Transporters