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Use of the CRISPR/Cas9 system as an intracellular defense against HIV-1 infection in human cells

Hsin-Kai Liao, Ying Gu, Arturo Diaz, John Marlett, Yuta Takahashi, Mo Li, Keiichiro Suzuki, Ruo Xu, Tomoaki Hishida, Chan-Jung Chang, Concepcion Rodriguez Esteban, John Young and Juan Carlos Izpisua Belmonte ()
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Hsin-Kai Liao: Gene Expression Laboratory, Salk Institute for Biological Studies
Ying Gu: Gene Expression Laboratory, Salk Institute for Biological Studies
Arturo Diaz: Nomis Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies
John Marlett: Nomis Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies
Yuta Takahashi: Gene Expression Laboratory, Salk Institute for Biological Studies
Mo Li: Gene Expression Laboratory, Salk Institute for Biological Studies
Keiichiro Suzuki: Gene Expression Laboratory, Salk Institute for Biological Studies
Ruo Xu: Biophysics and Molecular Biology, Iowa State University
Tomoaki Hishida: Gene Expression Laboratory, Salk Institute for Biological Studies
Chan-Jung Chang: Gene Expression Laboratory, Salk Institute for Biological Studies
Concepcion Rodriguez Esteban: Gene Expression Laboratory, Salk Institute for Biological Studies
John Young: Nomis Center for Immunobiology and Microbial Pathogenesis, Salk Institute for Biological Studies
Juan Carlos Izpisua Belmonte: Gene Expression Laboratory, Salk Institute for Biological Studies

Nature Communications, 2015, vol. 6, issue 1, 1-10

Abstract: Abstract To combat hostile viruses, bacteria and archaea have evolved a unique antiviral defense system composed of clustered regularly interspaced short palindromic repeats (CRISPRs), together with CRISPR-associated genes (Cas). The CRISPR/Cas9 system develops an adaptive immune resistance to foreign plasmids and viruses by creating site-specific DNA double-stranded breaks (DSBs). Here we adapt the CRISPR/Cas9 system to human cells for intracellular defense against foreign DNA and viruses. Using HIV-1 infection as a model, our results demonstrate that the CRISPR/Cas9 system disrupts latently integrated viral genome and provides long-term adaptive defense against new viral infection, expression and replication in human cells. We show that engineered human-induced pluripotent stem cells stably expressing HIV-targeted CRISPR/Cas9 can be efficiently differentiated into HIV reservoir cell types and maintain their resistance to HIV-1 challenge. These results unveil the potential of the CRISPR/Cas9 system as a new therapeutic strategy against viral infections.

Date: 2015
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7413

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DOI: 10.1038/ncomms7413

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