Gene Delivery of Alpha-1-Antitrypsin Using Recombinant Adeno-Associated Virus (rAAV)
Gene Delivery of Alpha-1-Antitrypsin Using Recombinant Adeno-Associated Virus (rAAV)
复制标题
DOI：
10.1007/978-1-4939-8645-3_12
复制
发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Lu, Yuanqing
中科院分区：
文献类型：
--
作者：
Song, Sihong;Lu, Yuanqing
α-1-抗胰蛋白酶（AAT，也称为SERPINA 1）基因治疗的挑战是实现长期和高水平的AAT生产。重组腺相关病毒（rAAV）载体用于AAT基因递送具有几个优点，包括载体中没有病毒基因、不需要整合用于长期转基因表达、低免疫原性和广泛嗜性。AAV介导的AAT基因疗法已经在AAT缺乏症、1型糖尿病、类风湿性关节炎和骨质疏松症的动物模型中开发和测试。AAV介导的AAT基因治疗也已在临床研究中进行了测试，并显示出有希望的结果。在这里，我们描述了rAAV-AAT载体的构建和生产方法，以及通过（1）肝脏定向，（2）肌肉定向和（3）间充质干细胞（MSC）介导的途径进行AAT基因递送的方法。我们还将描述用于评估每种递送方法的AAT表达的方法。
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.