CRISPR-Cas9基因编辑技术在病毒感染疾病治疗中的应用.pdf

Hereditas (Beijing) 2015 年 5 月, 37(5): 412―418 综 述 CRISPR-Cas9 基因编辑技术在病毒感染疾病治疗中的 应用 殷利眷，胡斯奇，郭斐 中国医学科学院/北京协和医学院病原生物学研究所，卫生部病原系统生物学重点实验室，北京 100730 摘要: CRISPR-Cas9 基因编辑技术是基于细菌或古细菌 CRISPR 介导的获得性免疫系统衍生而来，由一段 RNA 通过碱基互补配对识别 DNA，指导 Cas9 核酸酶切割识别的双链 DNA，诱发同源重组或非同源末端链接，进 而实现在目的 DNA 上进行编辑。病毒通过特异的受体侵染细胞，其基因组在细胞内发生复制、转录、翻译等 过程完成其生活周期，某些 DNA 病毒或逆转录病毒基因组会整合到宿主基因组中。基因治疗是病毒感染疾病 治疗的新趋势。因此，基因编辑技术在持续感染的病毒或潜伏感染病毒疾病治疗中具有重大的潜在意义。文章 主要从 CRISPR-Cas9 作用机制以及在病毒感染疾病治疗中的应用等方面进行了综述。 关键词?CRISPR；同源重组；非同源末端链接；基因编辑；病毒 The application of CRISPR-Cas9 gene editing technology in viral infection diseases Lijuan Yin, Siqi Hu, Fei Guo MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences Peking Union Medical College, Beijing 100730, China Abstract: The RNA-guided Cas9 nuclease from microbial clustered regularly interspaced short palindromic re- peats (CRISPR) adaptive immune system has been used to facilitate efficient genome engineering in eukaryotic cells. The specific targeted genome is recognized and cut by gRNA-directed CRISPR/Cas9 complex, specifically by the endonuclease Cas9. The targeted gene locus could be repaired either by homology-directed repair or nonhomologous end joining, thus achieving a desired editing outcome. Viruses infect cells through specific receptors, and then the viral genome is transcribed, replicated and translated to complete its life cycle. As a result, some DNA virus and re- trovirus genomes are integrated into the cellular genome. Gene therapy is a new trend to treat viral infected diseases. Given its designable sequence-specific editing of the targeted genome, CRISPR/Cas9 ha