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Retinal Degenerative Diseases pp 719–724Cite as

Gene Therapy for Stargardt Disease Associated with ABCA4 Gene

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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, the ABCA4 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 to ABCA4 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 the Abca4 -/- murine model. Excitingly, two Phase I/IIa clinical trials are underway to treat patients with ABCA4-associated Startgardt’s disease (STGD1). As a result of the development of these novel technologies, effective therapies for ABCA4-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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Authors and Affiliations

  1. 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

Authors
  1. Zongchao Han
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  2. Shannon M. Conley
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  3. Muna I. Naash
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Corresponding author

Correspondence to Muna I. Naash .

Editor information

Editors and Affiliations

  1. Department of Ophthalmology, University of Florida, Gainesville, Florida, USA

    John D. Ash

  2. University Hospital Zurich, Zurich, Switzerland

    Christian Grimm

  3. Cole Eye Institute at the Cleveland Clin Division of Ophthalmology, Cleveland, Ohio, USA

    Joe G. Hollyfield

  4. Dean A. McGee Eye Inst., University of Oklahoma Health Science Center, Oklahoma City, Oklahoma, USA

    Robert E. Anderson

  5. Beckman Vision Center, University of California, San Francisco School of Medicine, San Francisco, California, USA

    Matthew M. LaVail

  6. 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 with ABCA4 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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  • DOI: https://doi.org/10.1007/978-1-4614-3209-8_90

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3208-1

  • Online ISBN: 978-1-4614-3209-8

  • eBook Packages: MedicineMedicine (R0)

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