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rAAV Human Trial Experience

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Adeno-Associated Virus

Part of the book series: Methods in Molecular Biology ((MIMB,volume 807))

Abstract

Recombinant AAV vectors have been used in clinical trials since the mid-1990s, with over 300 subjects enrolled in studies. Although there are not yet licensed AAV products, there are several clear examples of clinical efficacy, and recombinant AAV vectors have a strong safety record after administration both locally and systemically. This chapter provides a review of two types of studies that have shown efficacy, including studies for Leber’s congenital amaurosis, a hereditary retinal degenerative disorder in which subretinal administration of AAV has shown efficacy in terms of improvement in multiple measures of visual/retinal function; and of Parkinson’s disease which has also shown improvement in clinical and imaging studies after gene transfer to the CNS. The chapter also provides a detailed review of the results of studies of gene therapy for hemophilia, in which short-term efficacy was achieved, but expression of the donated gene failed to persist, likely due to an immune response to the vector. Safety issues relating to AAV-mediated gene transfer are discussed, including a detailed review of the single death to have occurred in an AAV gene therapy trial (likely unrelated to the AAV vector), and of issues related to integration and insertional mutagenesis, risk of germline transmission, and risks related to immune responses to either vector or transgene product. Finally, protocols for determining the presence of vector DNA in body fluids using real-time quantitative PCR, and for isolating, cryopreserving, and testing peripheral blood mononuclear cells for interferon-γ (IFN-γ) responses to capsid are described in detail.

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Authors and Affiliations

  1. Howard Hughes Medical Institute, Philadelphia, PA, USA

    Katherine A. High

  2. The Children’s Hospital of Philadelphia, Philadelphia, PA, USA

    Katherine A. High

  3. UMR Inserm U745, Faculty of Pharmaceutical and Biological Sciences, University Paris Descartes-Sorbonne-Paris Cité, Paris, France

    Patrick Aubourg

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  1. Katherine A. High
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Correspondence to Katherine A. High .

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Editors and Affiliations

  1. Center of Excellence for Regenerative, Health Biotechnology (CERHB), University of Florida, Innovation Drive 13706, Alachua, 32615, Florida, USA

    Richard O. Snyder

  2. INSERM U649, Labo. Thérapie Génique, CHU Hôtel Dieu, bd. Jean Monnet 30, Nantes CX 1, 44035, France

    Philippe Moullier

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High, K.A., Aubourg, P. (2012). rAAV Human Trial Experience. In: Snyder, R., Moullier, P. (eds) Adeno-Associated Virus. Methods in Molecular Biology, vol 807. Humana Press. https://doi.org/10.1007/978-1-61779-370-7_18

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  • DOI: https://doi.org/10.1007/978-1-61779-370-7_18

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  • Publisher Name: Humana Press

  • Print ISBN: 978-1-61779-369-1

  • Online ISBN: 978-1-61779-370-7

  • eBook Packages: Springer Protocols

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