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Methods Mol Biol. 2018;1826:183-196. doi: 10.1007/978-1-4939-8645-3_12.

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

Author information

1
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA. shsong@cop.ufl.edu.
2
Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL, USA.

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.

KEYWORDS:

AAT deficiency; Adeno-associated virus (AAV); Alpha-1-antitrypsin (AAT); Gene delivery; Serpin

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