CRISPR/Cas9 system could provide a curative therapy for HIV

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New research from Temple University and the University of Pittsburgh (both PA, USA) has demonstrated that excision of HIV-1 DNA from infected cells in animal hosts could eliminate further infection. The study is the first to demonstrate HIV-1 replication can be halted, and the virus eliminated, utilizing gene editing CRISPR/Cas9 in vivo.

The research builds on a prior proof-of-concept study carried out by the team in 2016, where they utilized transgenic, rodent models to demonstrate HIV-1 DNA in the host genome could be eliminated with a CRISPR/Cas9 system delivered by a recombinant adeno-associated viral vector.

Lead author Wenhui Hu, from Temple University, commented: “Our new study is more comprehensive; we confirmed the data from our previous work and have improved the efficiency of our gene editing strategy. We also show that the strategy is effective in two additional mouse models, one representing acute infection in mouse cells and the other representing chronic, or latent, infection in human cells.”

The team reconfirmed previous results, demonstrating that their system reduced viral RNA expression by 60–95% in transgenic mice.  The group then went on to test the system in mice infected with the murine equivalent of HIV-1, EcoHIV. They utilized live bioluminescence imaging to visualizeHIV-1 infected cells, reporting  that treatment with a CRISPR/Cas9 system reduced systemic EcoHIV infection.

Author Kamel Khalil (Temple University) explained: “With EcoHIV mice, we were able to investigate the ability of the CRISPR/Cas9 strategy to block viral replication and potentially prevent systemic infection.”

Finally, the team tested the gene-editing system in humanized mouse model with HIV-1 infection. The researchers discovered that following treatment with the CRISPR/Cas9 system viral fragments were successfully excised from the host cells.

This study is the first to demonstrate in vivo excision of HIV-1 proviral DNA by a CRISPR/Cas9 system – it represents a significant step toward human clinical trials and a move towards a permanent cure for HIV infection.

Khalili concluded: “The next stage would be to repeat the study in primates, a more suitable animal model where HIV infection induces disease, in order to further demonstrate elimination of HIV-1 DNA in latently infected T cells and other sanctuary sites for HIV-1, including brain cells. Our eventual goal is a clinical trial in human patients.”

Sources: Yin C, Zhang, T Qu X et al. In Vivo Excision of HIV-1 Provirus by saCas9 and Multiplex Single-Guide RNAs in Animal Models. Mol. Therapy. doi:10.1016/j.ymthe.2017.03.012 (2017) (Epub ahead of print); www.templehealth.org/News/GeneEditingStrategyEliminatesHIV-1Infection/BRinLiveAnimalsTempleResearchersShow?id=3247&showBack=true&PageIndex=0&cid=13

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