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Genome modification of CXCR4 by Staphylococcus aureus Cas9 renders cells resistance to HIV-1 infection.
- Source :
- Retrovirology; 11/15/2017, Vol. 14, p1-12, 12p
- Publication Year :
- 2017
-
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<superscript>+</superscript> 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<superscript>+</superscript> 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<superscript>+</superscript> T cells using adeno-associated virus-delivered CRISPR/SaCas9 and disrupted CXCR4 expression. We also showed that CXCR4-edited primary CD4<superscript>+</superscript> 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- CXCR4 receptors
STAPHYLOCOCCUS aureus
HIV infections
T cells
CD4 antigen
Subjects
Details
- Language :
- English
- ISSN :
- 17424690
- Volume :
- 14
- Database :
- Complementary Index
- Journal :
- Retrovirology
- Publication Type :
- Academic Journal
- Accession number :
- 126256840
- Full Text :
- https://doi.org/10.1186/s12977-017-0375-0