重组腺相关病毒规模化生物包装技术.PDFVIP

生 物 工 程 学 报 Chin J Biotech 2009, November 25; 25(11): 1608-1613 journals.im.ac.cn Chinese Journal of Biotechnology ISSN 1000-3061 cjb@im.ac.cn © 2009 Institute of Microbiology, CAS CSM, All rights reserved 综 述 1,2 1,2 1,2 1,2 王峰 , 刁勇 , 肖卫东 , 许瑞安 1 , 362021 2 , 362021 : 重组腺相关病毒(Recombinant adeno-associated virus, rAAV)的诸多优点使其成为具有巨大潜力的人类基因治疗 载体。人类基因治疗临床前和临床研究以及基因治疗产品的市场化要求rAAV 载体生产的规模化。自 1989 年野生型的 腺相关病毒序列被 Samulski 报道以来, rAAV 的生产工艺已经从传统的质粒共转染发展到应用包装细胞系和生产细胞 系, 包装细胞也从“人体细胞” 衍化到 “ 昆虫细胞” 。目前 rAAV 的生产规模和病毒载体质量都完全可以符合临床应用 要求, 有效地促进rAAV 在基因治疗临床上的广泛运用。以下将着重介绍rAAV 规模化生物包装技术的发展趋势, 尤其 各种规模化生产系统的要点。 : 重组腺相关病毒, 生物技术, 人体, 昆虫, 细胞, 包装, 规模化生产 Large-scale production of recombinant adeno-associated virus (rAAV) Feng Wang1,2, Yong Diao1,2, Weidong Xiao1,2, and Ruian Xu1,2 1 Engineering Research Center of Molecular Medicine, Ministry of Education , Quanzhou 362021, China 2 Institute of Molecular Medicine , Huaqiao University, Quanzhou 362021, China Abstract: Recombinant adeno-associated virus has been proven to be a promising gene delivery vector for human gene therapy with many advantages. Successful applications of recombinant adeno-associated virus vectors in preclinical and clinical human gene therapies make it become a demanded product. A well-established and large-scale production system is therefore required. Since wild type of adeno-associated virus was well characterized in 1989, progress has been made. Particularly, package system of recombinant adeno-associated virus has been developed to use insect cell instead of human cell. These advances in