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Advances in AAV Vector Development for Gene Therapy in the Retina

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Retinal Degenerative Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 801))

Abstract

Adeno-associated virus (AAV) is a small, non-pathogenic dependovirus that has shown great potential for safe and long-term expression of a genetic payload in the retina. AAV has been used to treat a growing number of animal models of inherited retinal degeneration, though drawbacks—including a limited carrying capacity, slow onset of expression, and a limited ability to transduce some retinal cell types from the vitreous—restrict the utility of AAV for treating some forms of inherited eye disease. Next generation AAV vectors are being created to address these needs, through rational design efforts such as the creation of self-complementary AAV vectors for faster onset of expression and specific mutations of surface-exposed residues to increase transduction of viral particles. Furthermore, directed evolution has been used to create, through an iterative process of selection, novel variants of AAV with newly acquired, advantageous characteristics. These novel AAV variants have been shown to improve the therapeutic potential of AAV vectors, and further improvements may be achieved through rational design, directed evolution, or a combination of these approaches, leading to broader applicability of AAV and improved treatments for inherited retinal degeneration.

Authors Timothy P. Day and Leah C. Byrne contributed equally.

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Abbreviations

AAV:

Adeno-associated virus

ITR:

Inverted terminal repeats

RPE:

Retinal pigment epithelium

LCA2:

Leber’s congenital amaurosis type 2

scAAV:

Self-complementary adeno-associated virus

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Author information

Authors and Affiliations

  1. Helen Wills Neuroscience Institute, The University of California Berkeley, 112 Barker Hall, 94720, Berkeley, CA, USA

    Timothy P. Day, Leah C. Byrne, David V. Schaffer & John G. Flannery

  2. Department of Chemical and Biomolecular Engineering, The University of California, 94720-1462, Berkeley, CA, USA

    David V. Schaffer

Authors
  1. Timothy P. Day
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  2. Leah C. Byrne
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  3. David V. Schaffer
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  4. John G. Flannery
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Corresponding author

Correspondence to John G. Flannery .

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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Day, T., Byrne, L., Schaffer, D., Flannery, J. (2014). Advances in AAV Vector Development for Gene Therapy in the Retina. 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_86

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  • DOI: https://doi.org/10.1007/978-1-4614-3209-8_86

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-3208-1

  • Online ISBN: 978-1-4614-3209-8

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