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Gene Delivery of Alpha-1-Antitrypsin Using Recombinant Adeno-Associated Virus (rAAV)

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Serpins

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1826))

Abstract

The challenge for alpha-1-antitrypsin (AAT also known as SERPINA1) gene therapy is to achieve long term and high levels of AAT production. Recombinant adeno-associated virus (rAAV) vector has several advantages for AAT gene delivery including no viral genes in the vector, no requirement of integration for long-term transgene expression, low immunogenicity, and wide tropism. AAV-mediated AAT gene therapy has been developed and tested in animal models for AAT deficiency, type 1 diabetes, rheumatoid arthritis, and osteoporosis. AAV-mediated AAT gene therapy has also been tested in clinical studies and has shown promising results. Here we describe the methods of rAAV-AAT vector construction and production as well as AAT gene delivery through (1) liver-directed, (2) muscle-directed, and (3) mesenchymal stem cell (MSC)-mediated routes. We will also describe methods for the evaluation of AAT expression for each delivery approach.

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Authors and Affiliations

  1. Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA

    Sihong Song & Yuanqing Lu

Authors
  1. Sihong Song
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  2. Yuanqing Lu
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Corresponding author

Correspondence to Sihong Song .

Editor information

Editors and Affiliations

  1. Biodesign Center for Personalized Diagnostics and Center for Immunotherapy Vaccines and Virotherapy, Arizona State University, Tempe, AZ, USA

    Alexandra Lucas

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Song, S., Lu, Y. (2018). Gene Delivery of Alpha-1-Antitrypsin Using Recombinant Adeno-Associated Virus (rAAV). In: Lucas, A. (eds) Serpins. Methods in Molecular Biology, vol 1826. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-8645-3_12

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  • DOI: https://doi.org/10.1007/978-1-4939-8645-3_12

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  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-8644-6

  • Online ISBN: 978-1-4939-8645-3

  • eBook Packages: Springer Protocols

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