慢病毒载体系统及其安全性研究进展

Research Progress on Lentiviral Vector Systems and Their Safety Issue

慢病毒载体来源于人类免疫缺陷病毒,是一种强大的真核细胞基因修饰工具,有近30年的发展历史,多款基于慢病毒载体的CAR⁃T细胞疗法已获批上市,进一步推动了慢病毒载体的普及。但由于早期的慢病毒载体系统各质粒间或质粒与细胞基因组间可能发生重组而产生复制型慢病毒(Replication competent lentivirus,RCL),存在严重安全隐患,提高病毒载体安全性始终贯穿于整个病毒载体的改造历史。为保障慢病毒载体能安全有效地应用于临床,应对其质量进行充分研究。本文就慢病毒载体的改造历程进行综述,并介绍其在免疫细胞治疗中的应用及相关产品的质量研究,为慢病毒载体相关产品的质量和安全奠定基础。

Lentiviral vectors,derived from human immunodeficiency virus,are powerful tools for genetic modification of eukaryotic cells.With nearly 30 years of development history,several lentiviral vector⁃based chimeric antigen receptor T cell therapies have been approved and marketed,which further promote the use of lentiviral vectors.However,there are serious safety concerns because of the possibility of recombination among plasmids or plasmid⁃cell genomes of early lentiviral vector systems to produce replication competent lentivirus.Therefore,continuous improvement of the safety of viral vectors is critical.In order to make lentiviral vectors safe and effective for clinical trial,the quality of the product should be adequately investigated.This article reviews the development of lentiviral vectors,and introduces their application in immune cell therapy and quality research into related products,which lays the foundation for the quality and safety of lentiviral vector⁃related products.