CRISPR-Cas13a Inhibits HIV-1 Infection

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...

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Published in:Molecular therapy. Nucleic acids Vol. 21; pp. 147 - 155
Main Authors: Yin, Lijuan, Zhao, Fei, Sun, Hong, Wang, Zhen, Huang, Yu, Zhu, Weijun, Xu, Fengwen, Mei, Shan, Liu, Xiaoman, Zhang, Di, Wei, Liang, Cen, Shan, Hu, Siqi, Liang, Chen, Guo, Fei
Format: Journal Article
Language:English
Published: United States Elsevier Inc 04-09-2020
American Society of Gene & Cell Therapy
Elsevier
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Summary: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 CRISPR-Cas13a 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. [Display omitted] The class 2 type VI CRISPR-Cas effector Cas13a targets and cleaves RNA, providing protection against RNA phages. Yin et al. demonstrate that CRISPR-Cas13a targets and cleaves the HIV RNA genome and mRNA, leading to strong inhibition of HIV-1 infection.
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These authors contributed equally to this work.
ISSN:2162-2531
2162-2531
DOI:10.1016/j.omtn.2020.05.030