期刊
SCIENTIFIC REPORTS
卷 8, 期 -, 页码 -出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-26894-4
关键词
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资金
- Natural Science Foundation of China [81401659]
- China Postdoctoral Science Foundation [2015T80838, 2014M560622]
- China National Special Research Program of Major Infectious Diseases [2014ZX10001003]
- Hubei Provincial Science & Technology Innovation Team Grant [2012FFA043]
- Hubei Province's Outstanding Medical Academic Leader Program
- China Scholarship Council
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.
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