Retrovirology | |
The CRISPR/Cas9 system inactivates latent HIV-1 proviral DNA | |
Chen Liang2  Mark A Wainberg2  Fei Guo1  Jian Li1  Yann Le Duff2  Rongyue Lei1  Weijun Zhu1  | |
[1] MOH Key Laboratory of Systems Biology of Pathogens and AIDS Research Center, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100730, PR China;Departments of Medicine, Microbiology & Immunology, McGill University, Montreal H3A 2B4, Canada | |
关键词: Genome editing; CRISPR/Cas9; Reservoir; Provirus; HIV-1; | |
Others : 1162844 DOI : 10.1186/s12977-015-0150-z |
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received in 2014-11-25, accepted in 2015-02-09, 发布年份 2015 | |
【 摘 要 】
Background
Highly active antiretroviral therapy (HAART) has transformed HIV-1 infection from a deadly disease to a manageable chronic illness, albeit does not provide a cure. The recently developed genome editing system called CRISPR/Cas9 offers a new tool to inactivate the integrated latent HIV-1 DNA and may serve as a new avenue toward cure.
Findings
We tested 10 sites in HIV-1 DNA that can be targeted by CRISPR/Cas9. The engineered CRISPR/Cas9 system was introduced into the JLat10.6 cells that are latently infected by HIV-1. The sequencing results showed that each target site in HIV-1 DNA was efficiently mutated by CRISPR/Cas9 with the target site in the second exon of Rev (called T10) exhibiting the highest degree of mutation. As a result, HIV-1 gene expression and virus production were significantly diminished with T10 causing a 20-fold reduction.
Conclusions
The CRISPR/Cas9 complex efficiently mutates and deactivates HIV-1 proviral DNA in latently infected Jurkat cells. Our results also revealed a highly efficient Cas9 target site within the second exon of Rev that represents a promising target to be further explored in the CRISPR/Cas9-based cure strategy.
【 授权许可】
2015 Zhu et al.; licensee BioMed Central.
【 预 览 】
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Figure 1. | 65KB | Image | download |
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