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病毒载体遗传毒性评价方法研究进展

何伟伟 周长慧 郑明岚 李嫚琪 崔文腾 方雅励 王晓炜 常艳

中国药理学与毒理学杂志2024,Vol.38Issue(4):314-320,7.
中国药理学与毒理学杂志2024,Vol.38Issue(4):314-320,7.DOI:10.3867/j.issn.1000-3002.2024.04.009

病毒载体遗传毒性评价方法研究进展

Progress in genotoxicity evaluation methods of viral vectors

何伟伟 1周长慧 1郑明岚 2李嫚琪 1崔文腾 1方雅励 1王晓炜 3常艳1

作者信息

  • 1. 中国医药工业研究总院,上海益诺思生物技术股份有限公司,上海 201203
  • 2. 国家药品监督管理局药品审评检查长三角分中心,上海 201203
  • 3. 深圳市药品检验研究院,广东深圳 518057
  • 折叠

摘要

Abstract

With the gradual entry of gene therapy products into the market,there is an urgent need to establish viral vector-mediated genotoxicity evaluation methods.The two most widely used viral vectors are lentiviral vectors and adeno-associated viral vectors.Lentiviral vectors can stably integrate into the host genome while the viral vector genome mainly exists in the form of episomes in the nucleus of the host cell,and can still be randomly integrated into the host cell genome at a low frequency,the integra-tion modes for which include random integration and targeted integration.This paper reviews the existing methods for evaluating the genotoxicity mediated by viral vectors,including whole-genome analysis of off-target modifications,integration site analysis,karyotype analysis,and tests to assess the potential for cell transformation.This article also offers a vision of the establishment of an accurate and rapid evaluation system for viral vector-mediated genotoxicity in the hopes of providing reference for improvement and development of new methods for evaluating the genotoxicity of viral vectors.

关键词

基因治疗/病毒载体/整合/遗传毒性

Key words

gene therapy/viral vector/integration/genotoxicity

分类

医药卫生

引用本文复制引用

何伟伟,周长慧,郑明岚,李嫚琪,崔文腾,方雅励,王晓炜,常艳..病毒载体遗传毒性评价方法研究进展[J].中国药理学与毒理学杂志,2024,38(4):314-320,7.

基金项目

上海市科委研发公共服务平台项目(21DZ2291000) Shanghai Municipal Science and Technology Commission R&D Public Service Platform Project(21DZ2291000) (21DZ2291000)

中国药理学与毒理学杂志

OA北大核心CSTPCD

1000-3002

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