Genome editing of the HIV co-receptors CCR5 and CXCR4 by CRISPR-Cas9 protects CD4+ T cells from HIV-1 infection

Background The main approach to treat HIV-1 infection is combination antiretroviral therapy (cART). Although cART is effective in reducing HIV-1 viral load and controlling disease progression, it has many side effects, and is expensive for HIV-1 infected patients who must remain on lifetime treatment. HIV-1 gene therapy has drawn much attention as studies of genome editingtools have progressed. For example, zinc finger nucleases(ZFN), transcription activator like effector nucleases(TALEN) and clustered regularly interspaced short palindromicrepeats ( CRISPR)- Cas9have been utilized to successfully disrupt the HIV-1 co-receptorsCCR5 or CXCR4, thereby restricting HIV-1 infection. However, the effects of simultaneous genome editingof CXCR4and CCR5 by CRISPR- Cas9in blocking HIV-1 infection in primary CD4+ T cells has been rarely reported. Furthermore, combination of different target sites of CXCR4and CCR5 for disruption also need investigation.