Title |
RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection
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Published in |
Proceedings of the National Academy of Sciences of the United States of America, July 2014
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DOI | 10.1073/pnas.1405186111 |
Pubmed ID | |
Authors |
Wenhui Hu, Rafal Kaminski, Fan Yang, Yonggang Zhang, Laura Cosentino, Fang Li, Biao Luo, David Alvarez-Carbonell, Yoelvis Garcia-Mesa, Jonathan Karn, Xianming Mo, Kamel Khalili |
Abstract |
AIDS remains incurable due to the permanent integration of HIV-1 into the host genome, imparting risk of viral reactivation even after antiretroviral therapy. New strategies are needed to ablate the viral genome from latently infected cells, because current methods are too inefficient and prone to adverse off-target effects. To eliminate the integrated HIV-1 genome, we used the Cas9/guide RNA (gRNA) system, in single and multiplex configurations. We identified highly specific targets within the HIV-1 LTR U3 region that were efficiently edited by Cas9/gRNA, inactivating viral gene expression and replication in latently infected microglial, promonocytic, and T cells. Cas9/gRNAs caused neither genotoxicity nor off-target editing to the host cells, and completely excised a 9,709-bp fragment of integrated proviral DNA that spanned from its 5' to 3' LTRs. Furthermore, the presence of multiplex gRNAs within Cas9-expressing cells prevented HIV-1 infection. Our results suggest that Cas9/gRNA can be engineered to provide a specific, efficacious prophylactic and therapeutic approach against AIDS. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 39 | 18% |
Mexico | 29 | 13% |
United Kingdom | 13 | 6% |
Spain | 10 | 5% |
Germany | 4 | 2% |
France | 3 | 1% |
Canada | 2 | <1% |
Oman | 2 | <1% |
South Africa | 2 | <1% |
Other | 19 | 9% |
Unknown | 99 | 45% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 174 | 78% |
Scientists | 39 | 18% |
Science communicators (journalists, bloggers, editors) | 5 | 2% |
Practitioners (doctors, other healthcare professionals) | 4 | 2% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 23 | 3% |
Germany | 5 | <1% |
United Kingdom | 4 | <1% |
Japan | 4 | <1% |
Canada | 3 | <1% |
France | 2 | <1% |
South Africa | 2 | <1% |
Spain | 2 | <1% |
Mexico | 2 | <1% |
Other | 7 | <1% |
Unknown | 846 | 94% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Bachelor | 184 | 20% |
Student > Ph. D. Student | 178 | 20% |
Student > Master | 138 | 15% |
Researcher | 127 | 14% |
Student > Doctoral Student | 32 | 4% |
Other | 104 | 12% |
Unknown | 137 | 15% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 316 | 35% |
Biochemistry, Genetics and Molecular Biology | 200 | 22% |
Medicine and Dentistry | 71 | 8% |
Immunology and Microbiology | 59 | 7% |
Chemistry | 20 | 2% |
Other | 74 | 8% |
Unknown | 160 | 18% |