Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection

作者：Panpan Hou, Shuliang Chen, Shilei Wang, Xiao Lin Yu, Yu Zheng Chen, Meng Jiang, Ke Zhuang, Wen‐Zhe Ho, Wei Hou, Jian Yuan Huang, Deyin Guo · 发表于：Scientific Reports · 年份：2015 · DOI：10.1038/srep15577 · 被引用次数：217 · 研究领域：CRISPR and Genetic Engineering、HIV Research and Treatment、Mosquito-borne diseases and control

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.