Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection.
Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection.
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DOI：
10.1038/srep15577
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发表时间：
2015-10-20
影响因子：
4.6
通讯作者：
Guo D
中科院分区：
文献类型：
--
作者：
Hou P;Chen S;Wang S;Yu X;Chen Y;Jiang M;Zhuang K;Ho W;Hou W;Huang J;Guo D
通过CRISPR/Cas9进行基因组编辑已经成为一种有效可靠的方法，可以对活细胞的基因组进行精确的靶向改变。CXCR 4是人类免疫缺陷病毒1型（human immunodeficiency virus type 1，HIV-1）感染的共受体，被认为是艾滋病的重要治疗靶点。CXCR 4通过与包膜蛋白gp 120结合介导病毒进入人CD 4+细胞。在这里，我们发现人类CXCR 4基因被CRISPR/Cas9介导的基因组编辑有效破坏，导致人类原代CD 4 + T细胞的HIV-1抗性。我们还表明，Cas9介导的CXCR 4消融表现出高特异性和可忽略的脱靶效应，而不影响细胞分裂和繁殖。CXCR 4基因组的精确和高效编辑将为抗HIV-1感染的治疗应用提供新的策略。
Genome editing via CRISPR/Cas9 has become an efficient and reliable way to make precise, targeted changes to the genome of living cells. CXCR4 is a co-receptor for the human immunodeficiency virus type 1 (HIV-1) infection and has been considered as an important therapeutic target for AIDS. CXCR4 mediates viral entry into human CD4+ cells by binding to envelope protein, gp120. Here, we show that human CXCR4 gene is efficiently disrupted by CRISPR/Cas9-mediated genome editing, leading to HIV-1 resistance of human primary CD4+ T cells. We also show that the Cas9-mediated ablation of CXCR4 demonstrated high specificity and negligible off-target effects without affecting cell division and propagation. The precise and efficient genome editing of CXCR4 will provide a new strategy for therapeutic application against HIV-1 infection.