Gene Therapy of ABCA4-Associated Diseases
- PMID:25573774
- PMCID: PMC4448589
- DOI: 10.1101/cshperspect.a017301
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.
Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.
Similar articles
- Localization and functional characterization of the p.Asn965Ser (N965S) ABCA4 variant in mice reveal pathogenic mechanisms underlying Stargardt macular degeneration.Molday LL, Wahl D, Sarunic MV, Molday RS.Molday LL, et al.Hum Mol Genet. 2018 Jan 15;27(2):295-306. doi: 10.1093/hmg/ddx400.Hum Mol Genet. 2018.PMID:29145636Free PMC article.
- Expression of ABCA4 in the retinal pigment epithelium and its implications for Stargardt macular degeneration.Lenis TL, Hu J, Ng SY, Jiang Z, Sarfare S, Lloyd MB, Esposito NJ, Samuel W, Jaworski C, Bok D, Finnemann SC, Radeke MJ, Redmond TM, Travis GH, Radu RA.Lenis TL, et al.Proc Natl Acad Sci U S A. 2018 Nov 20;115(47):E11120-E11127. doi: 10.1073/pnas.1802519115. Epub 2018 Nov 5.Proc Natl Acad Sci U S A. 2018.PMID:30397118Free PMC article.
- Complement modulation in the retinal pigment epithelium rescues photoreceptor degeneration in a mouse model of Stargardt disease.Lenis TL, Sarfare S, Jiang Z, Lloyd MB, Bok D, Radu RA.Lenis TL, et al.Proc Natl Acad Sci U S A. 2017 Apr 11;114(15):3987-3992. doi: 10.1073/pnas.1620299114. Epub 2017 Mar 27.Proc Natl Acad Sci U S A. 2017.PMID:28348233Free PMC article.
- Insights into the Molecular Properties of ABCA4 and Its Role in the Visual Cycle and Stargardt Disease.Molday RS.Molday RS.Prog Mol Biol Transl Sci. 2015;134:415-31. doi: 10.1016/bs.pmbts.2015.06.008. Epub 2015 Jul 14.Prog Mol Biol Transl Sci. 2015.PMID:26310168Review.
- Stargardt-Fundus flavimaculatus: recent advancements and treatment.Haji Abdollahi S, Hirose T.Haji Abdollahi S, et al.Semin Ophthalmol. 2013 Sep-Nov;28(5-6):372-6. doi: 10.3109/08820538.2013.825286.Semin Ophthalmol. 2013.PMID:24138045Review.
Cited by
- Neovascular Age-Related Macular Degeneration (nAMD): A Review of Emerging Treatment Options.Tan CS, Ngo WK, Chay IW, Ting DS, Sadda SR.Tan CS, et al.Clin Ophthalmol. 2022 Mar 25;16:917-933. doi: 10.2147/OPTH.S231913. eCollection 2022.Clin Ophthalmol. 2022.PMID:35368240Free PMC article.Review.
- Localization and functional characterization of the p.Asn965Ser (N965S) ABCA4 variant in mice reveal pathogenic mechanisms underlying Stargardt macular degeneration.Molday LL, Wahl D, Sarunic MV, Molday RS.Molday LL, et al.Hum Mol Genet. 2018 Jan 15;27(2):295-306. doi: 10.1093/hmg/ddx400.Hum Mol Genet. 2018.PMID:29145636Free PMC article.
- Monitoring and Management of the Patient with Stargardt Disease.Cicinelli MV, Battista M, Starace V, Battaglia Parodi M, Bandello F.Cicinelli MV, et al.Clin Optom (Auckl). 2019 Nov 28;11:151-165. doi: 10.2147/OPTO.S226595. eCollection 2019.Clin Optom (Auckl). 2019.PMID:31819694Free PMC article.Review.
- Identification of novel pathogenicABCA4 variants in a Han Chinese family with Stargardt disease.Xiang Q, Cao Y, Xu H, Guo Y, Yang Z, Xu L, Yuan L, Deng H.Xiang Q, et al.Biosci Rep. 2019 Jan 15;39(1):BSR20180872. doi: 10.1042/BSR20180872. Print 2019 Jan 31.Biosci Rep. 2019.PMID:30563929Free PMC article.
- Losing, preserving, and restoring vision from neurodegeneration in the eye.Kerschensteiner D.Kerschensteiner D.Curr Biol. 2023 Oct 9;33(19):R1019-R1036. doi: 10.1016/j.cub.2023.08.044.Curr Biol. 2023.PMID:37816323Free PMC article.Review.
References
- Acland GM, Aguirre GD, Ray J, Zhang Q, Aleman TS, Cideciyan AV, Pearce-Kelling SE, Anand V, Zeng Y, Maguire AM, et al. 2001. Gene therapy restores vision in a canine model of childhood blindness. Nat Genet 28: 92–95. - PubMed
- Allikmets R, Singh N, Sun H, Shroyer NF, Hutchinson A, Chidambaram A, Gerrard B, Baird L, Stauffer D, Peiffer A, et al. 1997. A photoreceptor cell-specific ATP-binding transporter gene (ABCR) is mutated in recessive Stargardt macular dystrophy. Nat Genet 15: 236–246. - PubMed
- Allocca M, Tessitore A, Cotugno G, Auricchio A. 2006. AAV-mediated gene transfer for retinal diseases. Expert Opin Biol Ther 6: 1279–1294. - PubMed
Publication types
MeSH terms
Substances
Related information
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical