Genome modification of CXCR4 by Staphylococcus aureus Cas9 renders cells resistance to HIV-1 infection

Qiankun Wang; Shuliang Chen; Qiaoqiao Xiao; Zhepeng Liu; Shuai Liu; Panpan Hou; Li Zhou; Wei Hou; Wenzhe Ho; Chunmei Li; Li Wu; Deyin Guo

doi:10.1186/s12977-017-0375-0

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Genome modification of CXCR4 by Staphylococcus aureus Cas9 renders cells resistance to HIV-1 infection

Journal article

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Genome modification of CXCR4 by Staphylococcus aureus Cas9 renders cells resistance to HIV-1 infection

Qiankun Wang, Shuliang Chen, Qiaoqiao Xiao, Zhepeng Liu, Shuai Liu, Panpan Hou, Li Zhou, Wei Hou, Wenzhe Ho, Chunmei Li, …

Retrovirology, Vol.14(1), pp.51-51

11/15/2017

DOI: 10.1186/s12977-017-0375-0

PMCID: PMC5688617

PMID: 29141633

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Abstract

Background The CRISPR/Cas9 system has been widely used for genome editing in mammalian cells. CXCR4 is a co-receptor for human immunodeficiency virus type 1 (HIV-1) entry, and loss of CXCR4 function can protect cells from CXCR4 (X4)-tropic HIV-1 infection, making CXCR4 an important target for HIV-1 gene therapy. However, the large size of the CRISPR/SpCas9 system presents an obstacle to its efficient delivery into primary CD4+ T cells. Recently, a small Staphylococcus aureus Cas9 (SaCas9) has been developed as a genome editing tool can address this question. Therefore, it provides a promising strategy for HIV-1 gene therapy if it is used to target CXCR4. Results Here, we employed a short version of Cas9 from Staphylococcus aureus (SaCas9) for targeting CXCR4. We demonstrated that transduction of lenti-virus expressing SaCas9 and selected single-guided RNAs of CXCR4 in human CD4+ T cell lines efficiently induced the editing of the CXCR4 gene, making these cell lines resistant to X4-tropic HIV-1 infection. Moreover, we efficiently transduced primary human CD4+ T cells using adeno-associated virus-delivered CRISPR/SaCas9 and disrupted CXCR4 expression. We also showed that CXCR4-edited primary CD4+ T cells proliferated normally and were resistant to HIV-1 infection. Conclusions Our study provides a basis for possible application of CXCR4-targeted genome editing by CRISPR/SaCas9 in HIV-1 gene therapy.

HIV-1

CRISPR

Adeno-associated virus

CXCR4

Primary CD4+ T cells

Research

SaCas9

Details

Title: Subtitle: Genome modification of CXCR4 by Staphylococcus aureus Cas9 renders cells resistance to HIV-1 infection
Creators: Qiankun Wang - Wuhan, 430072 People’s Republic of China
Shuliang Chen - 1900 Coffey Road, Columbus, OH USA
Qiaoqiao Xiao - Wuhan, 430072 People’s Republic of China
Zhepeng Liu - Wuhan, 430072 People’s Republic of China
Shuai Liu - Wuhan, 430072 People’s Republic of China
Panpan Hou - Wuhan, People’s Republic of China
Li Zhou - Wuhan, People’s Republic of China
Wei Hou - Wuhan, 430072 People’s Republic of China
Wenzhe Ho - Wuhan, 430072 People’s Republic of China
Chunmei Li - Zhongshan Erlu 74, Yuexiu District, Guangzhou, 510080 People’s Republic of China
Li Wu - 1900 Coffey Road, Columbus, OH USA
Deyin Guo - Zhongshan Erlu 74, Yuexiu District, Guangzhou, 510080 People’s Republic of China
Resource Type: Journal article
Publication Details: Retrovirology, Vol.14(1), pp.51-51
DOI: 10.1186/s12977-017-0375-0
PMID: 29141633
PMCID: PMC5688617
NLM abbreviation: Retrovirology
ISSN: 1742-4690
eISSN: 1742-4690
Publisher: BioMed Central; London
Grant note: ; 2012FFA043 / ; 2014ZX10001003 / ; 2015T80838; 2014M560622 / ; AI104483; AI127667; AI120209 / ; 81401659 / ;
Language: English
Date published: 11/15/2017
Academic Unit: Microbiology and Immunology
Record Identifier: 9984001110302771

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