机构：[1]Department of Neuroscience, Center for Neurovirology and The Comprehensive NeuroAIDS Center, Temple University School of Medicine, Philadelphia, PA 19140[2]Cancer Genome Institute, Fox Chase Cancer Center, Temple University School of Medicine, Philadelphia, PA 19111[3]Department of Molecular Biology and Microbiology, Case Western Reserve University, Cleveland, OH 44106[4]Laboratory of Stem Cell Biology, State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu 610041, China四川大学华西医院
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.
基金：
National Institutes of Health Grants R01MH093271 (to K.K.), R01NS087971
(to W.H. and K.K.), and P30MH092177 (to K.K.).
语种：
外文
PubmedID：
中科院(CAS)分区：
出版当年[2014]版：
大类|1 区综合性期刊
小类|1 区综合性期刊
最新[2023]版：
大类|1 区综合性期刊
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第一作者：
第一作者机构：[1]Department of Neuroscience, Center for Neurovirology and The Comprehensive NeuroAIDS Center, Temple University School of Medicine, Philadelphia, PA 19140
共同第一作者：
通讯作者：
推荐引用方式(GB/T 7714)：
Hu Wenhui,Kaminski Rafal,Yang Fan,et al.RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection.[J].Proceedings of the National Academy of Sciences of the United States of America.2014,111(31):11461-6.doi:10.1073/pnas.1405186111.
APA：
Hu Wenhui,Kaminski Rafal,Yang Fan,Zhang Yonggang,Cosentino Laura...&Khalili Kamel.(2014).RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection..Proceedings of the National Academy of Sciences of the United States of America,111,(31)
MLA：
Hu Wenhui,et al."RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection.".Proceedings of the National Academy of Sciences of the United States of America 111..31(2014):11461-6
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