Harnessing the CRISPR/Cas9 system to disrupt latent HIV-1 provirus

被引:430
作者
Ebina, Hirotaka [1 ]
Misawa, Naoko [1 ]
Kanemura, Yuka [1 ]
Koyanagi, Yoshio [1 ]
机构
[1] Kyoto Univ, Inst Virus Res, Lab Viral Pathogenesis, Sakyo Ku, Kyoto 6068507, Japan
来源
SCIENTIFIC REPORTS | 2013年 / 3卷
基金
日本学术振兴会;
关键词
REAL-TIME PCR; GENOME; COMPLEX; INTEGRATION; EFFICIENCY; INFECTION; NUCLEASE; CELLS;
D O I
10.1038/srep02510
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Even though highly active anti-retroviral therapy is able to keep HIV-1 replication under control, the virus can lie in a dormant state within the host genome, known as a latent reservoir, and poses a threat to re-emerge at any time. However, novel technologies aimed at disrupting HIV-1 provirus may be capable of eradicating viral genomes from infected individuals. In this study, we showed the potential of the CRISPR/Cas9 system to edit the HIV-1 genome and block its expression. When LTR-targeting CRISPR/Cas9 components were transfected into HIV-1 LTR expression-dormant and -inducible T cells, a significant loss of LTR-driven expression was observed after stimulation. Sequence analysis confirmed that this CRISPR/Cas9 system efficiently cleaved and mutated LTR target sites. More importantly, this system was also able to remove internal viral genes from the host cell chromosome. Our results suggest that the CRISPR/Cas9 system may be a useful tool for curing HIV-1 infection.
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页数:7
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