Abstract
Despite the fact that great efforts have been made in the prevention and therapy of HIV-1 infection, HIV-1/AIDS remains a major threat to global human health. Highly active antiretroviral therapy (HAART) can suppress virus replication, but it cannot eradicate latent viral reservoirs in HIV-1/AIDS patients. Recently, the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) system has been engineered as an effective gene-editing technology with the potential to treat HIV-1/AIDS. It can be used to target cellular co-factors or HIV-1 genome to reduce HIV-1 infection and clear the provirus, as well as to induce transcriptional activation of latent virus in latent viral reservoirs for elimination. This versatile gene editing technology has been successfully applied to HIV-1/AIDS prevention and reduction in human cells and animal models. Here, we update the rapid progress of CRISPR/Cas9-based HIV-1/AIDS therapy research in recent years and discuss the limitations and future perspectives of its application.
Highlights
Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is still a severe health problem worldwide
We summarize studies concerning the principles, function, and application of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated nuclease 9 (Cas9) in HIV1/AIDS treatment in the last few years, and highlight problems that need to be addressed in the future
With the development of gene editing technologies, such as zinc finger nucleases (ZFNs), transcription activator-like nucleases (TALENs) and CRISPR/Cas9, more and more recent work focuses on using these new strategies to eliminate the virus in patients
Summary
Human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) is still a severe health problem worldwide. NONO directly interacted with HIV-1/2 capsid proteins to increase DNA sensing mediated by cGAS but had little effect on HIV infection, which suggest the important role of NONO in cGAS-mediated immune activation after infection with HIV (Lahaye et al, 2018) Since these representative restriction factors can inhibit HIV infection via different mechanisms, the CRISPR/Cas technology could be used to simultaneously activate their expression in infected cells in order to target different phases of the viral life cycle. This approach may provide new strategies for the treatment of HIV-1 infection, and more efforts are needed to further develop this toolset. Whether its activated expression in different cells over a long period of time has deleterious effects in vivo has not been reported at present
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