Abstract:

Lentiviral vectors have been widely used to transfer exogenous DNA into human cells to treat various genetic diseases. Lentiviral vectors can integrate into the host genome， but their integration sites are often unpredictable， which may increase the uncertainty of their therapeutic efficacy. With the wide application of gene and cell therapy， regulators have also issued a series of technical guidance documents to ensure the continuous safety of products. Integration site analysis （ISA） is a key tool for evaluating the biological safety of gene therapy vectors by characterizing their integration profiles， as well as for tracking transgenic cells. This review mainly described the technological evolution of integration sites for retroviruses， and the advantages and development trends of analysis methods. At the same time， strategies to reduce the random integration of viruses into the genome were also reviewed， in order to provide reference for the analysis and detection of lentiviral vector integration as a point of view and the safety evaluation of new drug clinical trials in cell therapy products.

Key words: integration site analysis, information analysis tools, biosafety, gene and cell therapy

摘要：

慢病毒载体已被广泛用于将外源DNA转移到人类细胞中治疗各种遗传疾病。慢病毒载体可以整合到宿主基因组中，但整合位点通常不可预测，这可能会增加其治疗效果的不确定性。随着基因及细胞疗法的广泛应用，监管机构出台了一系列技术指导文件，以确保产品持续的安全性。整合位点分析（integration site analysis，ISA）是通过表征基因治疗载体的整合图谱来评估其生物安全性，也是转基因细胞进行克隆跟踪的关键工具。概述了用于逆转录病毒整合位点的技术演变，以及信息分析工具的优势和发展趋势，总结了减低病毒随机整合至基因组中的应对策略，以期为慢病毒载体的整合位点分析检测和细胞治疗产品新药临床试验安全性评估提供参考。

关键词: 整合位点分析, 信息分析工具, 生物安全性, 基因及细胞疗法