Journal article
HIV-1 inhibition in cells with CXCR4 mutant genome created by CRISPR-Cas9 and piggyBac recombinant technologies
Scientific reports, Vol.8(1), 8573
06/05/2018
DOI: 10.1038/s41598-018-26894-4
PMID: 29872154
Abstract
The C-X-C chemokine receptor type 4 (CXCR4) is one of the major co-receptors for human immunodeficiency virus type 1 (HIV-1) entry and is considered an important therapeutic target. However, its function in maintaining the development of hematopoietic stem cells (HSC) makes it difficult to be used for HIV-1 gene therapy with HSC transplantation. A previous report showed that the natural CXCR4 P191A mutant inhibits HIV-1 infection without any defect in HSC differentiation, which could provide a basis for the development of new approaches for HIV-1 gene therapy. In the present study, we used CRISPR-Cas9 combined with the piggyBac transposon technologies to efficiently induce the expression of the CXCR4 P191A mutant in an HIV-1 reporter cell line, leading to no detectable exogenous sequences. In addition, no off-target effects were detected in the genome-edited cells. The decline of HIV-1 replication in biallelic CXCR4 gene-edited cells suggests that individuals equipped with homologous recombination of the CXCR4 P191A mutant could prevent or reduce HIV-1 infection. This study provides an effective approach to create a CXCR4 mutation with HIV-1 infection inhibition function and without leaving any genetic footprint inside cells, thereby shedding light on an application in HIV-1 gene therapy and avoiding side effects caused by deficiency or destruction of CXCR4 function.
Details
- Title: Subtitle
- HIV-1 inhibition in cells with CXCR4 mutant genome created by CRISPR-Cas9 and piggyBac recombinant technologies
- Creators
- Shuai Liu - School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, P.R. ChinaQiankun Wang - School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, P.R. ChinaXiao Yu - Institute of health inspection and testing, Hubei Provincial Center for Disease Control and Prevention, Wuhan, 430079, P.R. ChinaYilin Li - School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, P.R. ChinaYandan Guo - School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, P.R. ChinaZhepeng Liu - School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, P.R. ChinaFuyun Sun - School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, P.R. ChinaWei Hou - School of Basic Medical Sciences, Wuhan University, Wuhan, 430071, P.R. ChinaChunmei Li - School of Medicine (Shenzhen), Sun Yat-sen University, Guangzhou, 510080, P.R. ChinaLi Wu - Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, 43210, USADeyin Guo - School of Medicine (Shenzhen), Sun Yat-sen University, Guangzhou, 510080, P.R. China. guodeyin@mail.sysu.edu.cnShuliang Chen - Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University, Columbus, OH, 43210, USA. Chen-shuliang@whu.edu.cn
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.8(1), 8573
- DOI
- 10.1038/s41598-018-26894-4
- PMID
- 29872154
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- England
- Language
- English
- Date published
- 06/05/2018
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984002379502771
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