CRISPR-Cas13a Inhibits HIV-1 Infection

被引:49
|
作者
Yin, Lijuan [1 ,2 ]
Zhao, Fei [1 ,2 ]
Sun, Hong [1 ,2 ]
Wang, Zhen [3 ]
Huang, Yu [1 ,2 ]
Zhu, Weijun [1 ,2 ]
Xu, Fengwen [1 ,2 ]
Mei, Shan [1 ,2 ]
Liu, Xiaoman [1 ,2 ]
Zhang, Di [1 ,2 ]
Wei, Liang [1 ,2 ]
Cen, Shan [4 ]
Hu, Siqi [1 ,2 ]
Liang, Chen [3 ]
Guo, Fei [1 ,2 ]
机构
[1] Chinese Acad Med Sci & Peking Union Med Coll, NHC Key Lab Syst Biol Pathogens, Inst Pathogen Biol, Beijing 100730, Peoples R China
[2] Chinese Acad Med Sci & Peking Union Med Coll, Ctr AIDS Res, Beijing 100730, Peoples R China
[3] McGill Univ, Jewish Gen Hosp, AIDS Ctr, Lady Davis Inst, Montreal, PQ H3T 1E2, Canada
[4] Chinese Acad Med Sci & Peking Union Med Coll, Inst Med Biotechnol, Beijing 100005, Peoples R China
来源
基金
中国国家自然科学基金; 加拿大健康研究院;
关键词
SMALL INTERFERING RNA; T-CELLS; IMMUNE-SYSTEM; GENE-THERAPY; DISTINCT; CRISPR; EVOLUTION; DELIVERY; CLASSIFICATION; CLEAVAGE;
D O I
10.1016/j.omtn.2020.05.030
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
CRISPR-Cas provides bacteria and archaea with immunity against invading phages and foreign plasmid DNA and has been successfully adapted for gene editing in a variety of species. The class 2 type VI CRISPR-Cas effector Cas13a targets and cleaves RNA, providing protection against RNA phages. Here we report the repurposing of CRISPR-Cas13a to inhibit human immunodeficiency virus type 1 (HIV-1) infection through targeting HIV-1 RNA and diminishing viral gene expression. We observed strong inhibition of HIV-1 infection by CRISPR-Cas13a in human cells. We showed that CRISPRCas13a not only diminishes the level of newly synthesized viral RNA, either from the transfected plasmid DNA or from the viral DNA, which is integrated into cellular DNA, but it also targets and destroys the viral RNA that enters cells within viral capsid, leading to strong inhibition of HIV-1 infection. Together, our results suggest that CRISPR-Cas13a provides a potential novel tool to treat viral diseases in humans.
引用
收藏
页码:147 / 155
页数:9
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