重组腺相关病毒规模化生物包装技术

Large-scale production of recombinant adeno-associated virus (rAAV)

摘要:

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。

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 adeno-associated virus production will allow it to meet the demands of basic research and clinical applications. This review will focus on trends in packaging systems and development on a large scale of recombinant adeno- associated virus production.