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rAAV Human Trial Experience

  • Katherine A. HighEmail author
  • Patrick Aubourg
Protocol
Part of the Methods in Molecular Biology book series (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.

Key words

AAV Hemophilia B Leber’s congenital amaurosis Parkinson’s disease Rheumatoid arthritis Disseminated histoplasmosis Hepatocellular carcinoma IFN-γ ELISpot PBMCs 

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Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Howard Hughes Medical InstitutePhiladelphiaUSA
  2. 2.The Children’s Hospital of PhiladelphiaPhiladelphiaUSA
  3. 3.UMR Inserm U745, Faculty of Pharmaceutical and Biological SciencesUniversity Paris Descartes-Sorbonne-Paris CitéParisFrance

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