Zinc-finger-nucleases mediate specific and efficient excision of HIV-1 proviral DNA from infected and latently infected human T cells.
Zinc-finger-nucleases mediate specific and efficient excision of HIV-1 proviral DNA from infected and latently infected human T cells.
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锌指核酸酶介导从感染和潜伏感染的人类 T 细胞中特异性、高效地切除 HIV-1 前病毒 DNA
DOI：
10.1093/nar/gkt571
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发表时间：
2013-09
影响因子：
14.9
通讯作者：
Zhu H
中科院分区：
文献类型：
--
作者：
Qu X;Wang P;Ding D;Li L;Wang H;Ma L;Zhou X;Liu S;Lin S;Wang X;Zhang G;Liu S;Liu L;Wang J;Zhang F;Lu D;Zhu H
目前无法完全治愈HIV感染的个体，因为现有的抗病毒治疗方案并未解决已在这里整合到宿主基因组中的长期重复序列（LTRS）的艾滋病毒病毒DNA（LTRS），我们在这里呈现了一种可能的替代性治疗方法，以专门介导的全长HIV Intrestion tementions Humthem oftress Intrestions Intrestions Intrestions Intrestions Trimentimentimentions tatementions Trimentimentimentions。 Nucleases (ZFNs) to target a sequence within the LTR that is well constituted across all clades. We designed and screened one pair of ZFN to target the highly constituted HIV-1 5'-LTR and 3'-LTR DNA sequences, named ZFN-LTR. We found that ZFN-LTR can specifically target and clear the full-length HIV-1 proviral DNA in several infected and latently infected cell types and also HIV-1 infected human primary cells in vitro.我们观察到，在用ZFN-LTR处理后，感染的人类细胞系的惊喜频率为45.9％，而没有明显的宿主基因毒性，我们的数据表明，单个ZFN-LTR对可以专门有效地清除全长的HIV-1 Profiral DNA和中位数抗病毒感染，并建议在这种策略中提供一项策略，以提供一项策略。未来感染宿主的HIV-1病毒。
HIV-infected individuals currently cannot be completely cured because existing antiviral therapy regimens do not address HIV provirus DNA, flanked by long terminal repeats (LTRs), already integrated into host genome. Here, we present a possible alternative therapeutic approach to specifically and directly mediate deletion of the integrated full-length HIV provirus from infected and latently infected human T cell genomes by using specially designed zinc-finger nucleases (ZFNs) to target a sequence within the LTR that is well conserved across all clades. We designed and screened one pair of ZFN to target the highly conserved HIV-1 5′-LTR and 3′-LTR DNA sequences, named ZFN-LTR. We found that ZFN-LTR can specifically target and cleave the full-length HIV-1 proviral DNA in several infected and latently infected cell types and also HIV-1 infected human primary cells in vitro. We observed that the frequency of excision was 45.9% in infected human cell lines after treatment with ZFN-LTR, without significant host-cell genotoxicity. Taken together, our data demonstrate that a single ZFN-LTR pair can specifically and effectively cleave integrated full-length HIV-1 proviral DNA and mediate antiretroviral activity in infected and latently infected cells, suggesting that this strategy could offer a novel approach to eradicate the HIV-1 virus from the infected host in the future.
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影响因子：
46.9
作者：
Hockemeyer, Dirk;Soldner, Frank;Beard, Caroline;Gao, Qing;Mitalipova, Maisam;DeKelver, Russell C.;Katibah, George E.;Amora, Ranier;Boydston, Elizabeth A.;Zeitler, Bryan;Meng, Xiangdong;Miller, Jeffrey C.;Zhang, Lei;Rebar, Edward J.;Gregory, Philip D.;Urnov, Fyodor D.;Jaenisch, Rudolf
通讯作者：
Jaenisch, Rudolf
DOI：
10.1073/pnas.94.24.13193
发表时间：
1997-11-25
影响因子：
11.1
作者：
Chun, TW;Stuyver, L;Fauci, AS
通讯作者：
Fauci, AS
影响因子：
5.4
作者：
Eberhardy, SR;Goncalves, J;Barbas, CF
通讯作者：
Barbas, CF
影响因子：
7
作者：
Lee, Hyung Joo;Kim, Eunji;Kim, Jin-Soo
通讯作者：
Kim, Jin-Soo
影响因子：
56.9
作者：
Bibikova, M;Beumer, K;Carroll, D
通讯作者：
Carroll, D