Genome editing of CXCR4 by CRISPR/cas9 confers cells resistant to HIV-1 infection.
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.
School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, PR China.|College of Life Sciences, Wuhan University, Wuhan, 430072, PR China.
Panpan
P
Hou
School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, PR China.
Shuliang
S
Chen
College of Life Sciences, Wuhan University, Wuhan, 430072, PR China.
Shilei
S
Wang
College of Life Sciences, Wuhan University, Wuhan, 430072, PR China.
Xiao
X
Yu
College of Life Sciences, Wuhan University, Wuhan, 430072, PR China.
Yu
Y
Chen
Renmin Hospital of Wuhan University, Wuhan 430060, PR China.
Meng
M
Jiang
The Center for Animal Experiment and ABSL-3 Laboratory, Wuhan University School of Medicine, Wuhan, 430071, PR China.
Ke
K
Zhuang
The Center for Animal Experiment and ABSL-3 Laboratory, Wuhan University School of Medicine, Wuhan, 430071, PR China.
Wenzhe
W
Ho
School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, PR China.
Wei
W
Hou
Department of Pathology and Laboratory Medicine, School of Medicine, Temple University, Philadelphia, PA 19103.
Jian
J
Huang
School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, PR China.
Deyin
D
Guo
D000483:Alleles; D000818:Animals; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000821:virology; D064113:CRISPR-Cas Systems / Q000235:genetics; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D060467:Disease Resistance / Q000235:genetics*; D017353:Gene Deletion; D015870:Gene Expression; D018390:Gene Targeting; D056426:Genetic Loci; D015658:HIV Infections / Q000235:genetics* / Q000821:virology*; D015497:HIV-1; D006801:Humans; D019169:Jurkat Cells; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D017393:RNA Editing; D019718:Receptors, CXCR4 / Q000235:genetics* / Q000378:metabolism
D019718:Receptors, CXCR4