Snyder Richard O, Audit Muriel, Francis Joyce D
Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville, FL, USA.
Methods Mol Biol. 2011;807:405-28. doi: 10.1007/978-1-61779-370-7_17.
Recombinant adeno-associated viral (rAAV) vectors mediate the safe and long-term correction of genetic diseases following a single administration. Preclinical studies in animal models and human trials have shown rAAV vector persistence and safety. In some trials, sustained or transient transgene expression has been demonstrated in humans treated for alpha-1 antitrypsin deficiency, LPL deficiency, hemophilia B and cystic fibrosis, and sustained correction of inherited blindness has been reported by three groups. For human use, rAAV vectors are manufactured and tested in compliance with current Good Manufacturing Practices as outlined in the Code of Federal Regulations (21CFR) or European Good Manufacturing Practices (Eudralex, Volume 4, GMP Guidelines, 2003/94/CE and 91/356/EEC). Manufacturing control, as well as product quality is evaluated by quality control testing and all manufacturing, facilities, and testing activities are reviewed by the quality assurance department. In-process specifications are set and in-process testing is conducted to confirm that the manufacturing process is controlled, aseptic, and performs consistently. Final product is tested to ensure release specifications are met for identity, safety, purity, potency, and stability.
重组腺相关病毒（rAAV）载体单次给药后可介导对遗传疾病的安全且长期的矫正。在动物模型中的临床前研究和人体试验已表明rAAV载体的持久性和安全性。在一些试验中，已在接受治疗的α-1抗胰蛋白酶缺乏症、脂蛋白脂肪酶缺乏症、血友病B和囊性纤维化患者中证明了持续或短暂的转基因表达，并且有三个研究小组报告了遗传性失明的持续矫正情况。对于人类使用，rAAV载体按照《联邦法规》（21CFR）或欧洲药品生产质量管理规范（Eudralex，第4卷，GMP指南，2003/94/CE和91/356/EEC）中概述的现行药品生产质量管理规范进行生产和测试。通过质量控制测试评估生产控制以及产品质量，并且质量保证部门会审查所有生产、设施和测试活动。设定过程中的规范并进行过程中测试，以确认生产过程受到控制、无菌且性能一致。对最终产品进行测试，以确保其在身份、安全性、纯度、效力和稳定性方面符合放行规范。
