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

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 integrati...

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Bibliographic Details
Published inMethods in molecular biology (Clifton, N.J.) Vol. 1826; p. 183
Main Authors Song, Sihong, Lu, Yuanqing
Format Journal Article
LanguageEnglish
Published United States 01.01.2018
Subjects
Adeno-associated virus (AAV)
Alpha-1-antitrypsin (AAT)
Gene delivery
Serpin
AAT deficiency
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Summary: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.
ISSN:1940-6029
DOI:10.1007/978-1-4939-8645-3_12