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

• Published in: Scientific reports Vol. 5; no. 1; p. 15577
• Main Authors: Hou, Panpan, Chen, Shuliang, Wang, Shilei, Yu, Xiao, Chen, Yu, Jiang, Meng, Zhuang, Ke, Ho, Wenzhe, Hou, Wei, Huang, Jian, Guo, Deyin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20-10-2015; Nature Publishing Group
• Subjects: 13/109; 13/31; 38/77; 42/109; 42/44; 42/70; 45/23; 45/41; 631/61/201/2110; 692/699/255/1901; 96/1; 96/34; Acquired immune deficiency syndrome; AIDS; Alleles; Animals; Base Sequence; CD4 antigen; CD4-Positive T-Lymphocytes - metabolism; CD4-Positive T-Lymphocytes - virology; Cell division; Cell Line; Cell Membrane - metabolism; Cells, Cultured; CRISPR; CRISPR-Cas Systems - genetics; CXCR4 protein; Disease Resistance - genetics; Gene Deletion; Gene Expression; Gene Targeting; Genetic Loci; Genome editing; Genomes; Glycoprotein gp120; HIV; HIV Infections - genetics; HIV Infections - virology; HIV-1; Human immunodeficiency virus; Humanities and Social Sciences; Humans; Infections; Jurkat Cells; Lymphocytes T; Macaca mulatta; Molecular Sequence Data; multidisciplinary; Receptors, CXCR4 - genetics; Receptors, CXCR4 - metabolism; RNA Editing; Science; Viral envelope proteins
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep15577

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.