Part of the book series:Advances in Experimental Medicine and Biology ((AEMB,volume 801))
Abstract
Mutations in the photoreceptor-specific flippase ABCA4 lead to accumulation of the toxic bisretinoid A2E, resulting in atrophy of the retinal pigment epithelium (RPE) and death of the photoreceptor cells. Many blinding diseases are associated with these mutations including Stargardt’s disease (STGD1), cone-rod dystrophy, retinitis pigmentosa (RP), and increased susceptibility to age-related macular degeneration. There are no curative treatments for any of these dsystrophies. While the monogenic nature of many of these conditions makes them amenable to treatment with gene therapy, theABCA4 cDNA is 6.8 kb and is thus too large for the AAV vectors which have been most successful for other ocular genes. Here we review approaches toABCA4 gene therapy including treatment with novel AAV vectors, lentiviral vectors, and non-viral compacted DNA nanoparticles. Lentiviral and compacted DNA nanoparticles in particular have a large capacity and have been successful in improving disease phenotypes in theAbca4-/- murine model. Excitingly, two Phase I/IIa clinical trials are underway to treat patients withABCA4-associated Startgardt’s disease (STGD1). As a result of the development of these novel technologies, effective therapies forABCA4-associated diseases may finally be within reach.
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Acknowledgment
This work was supported by the NIH, the Foundation Fighting Blindness and the Oklahoma Center for the Advancement of Science and Technology.
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Department of Cell Biology, University of Oklahoma Health Sciences Center, 940 Stanton L. Young Blvd., BMSB 781, 73104, Oklahoma City, OK, USA
Zongchao Han, Shannon M. Conley & Muna I. Naash
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Correspondence toMuna I. Naash.
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Editors and Affiliations
Department of Ophthalmology, University of Florida, Gainesville, Florida, USA
John D. Ash
University Hospital Zurich, Zurich, Switzerland
Christian Grimm
Cole Eye Institute at the Cleveland Clin Division of Ophthalmology, Cleveland, Ohio, USA
Joe G. Hollyfield
Dean A. McGee Eye Inst., University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA
Robert E. Anderson
Beckman Vision Center, University of California, San Francisco School of Medicine, San Francisco, California, USA
Matthew M. LaVail
Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA
Catherine Bowes Rickman
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Han, Z., Conley, S., Naash, M. (2014). Gene Therapy for Stargardt Disease Associated withABCA4 Gene. In: Ash, J., Grimm, C., Hollyfield, J., Anderson, R., LaVail, M., Bowes Rickman, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 801. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-3209-8_90
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