Last year, researchers at Temple University and the University of Pittsburgh unveiled a proof-of-concept study that described how the CRISPR-Cas9 gene-editing tool could be used to eliminate HIV from infected cells. Now, in another potential step towards a permanent cure, the team has demonstrated that the technique works to keep the virus from spreading and, in latent cases, rips it from its hideout.

HIV is a tricky foe. When it's not actively spreading through the body, the virus likes to lay low inside cells where it can escape detection, and once it's in there it's hard to get rid of. Using three different animal models, the researchers showed that their gene-editing process can help fight the disease on both fronts.

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CRISPR-Cas9 is a genetic toolkit that can be programmed to target certain sequences of an organism's DNA, snip them out and replace them with something else. The process is already showing promise in combating cancer, controlling pests and improving crops, and in this case, the researchers have targeted fragments of HIV-1 DNA and cut them out of the host cells' genome.

Building on their previous work, the researchers improved their delivery system so it could target more cell types, and used four guide RNAs (molecules that help find the targeted DNA sequences in the genome) instead of just one previously. This makes it more efficient at locating and removing the virus.

Rather than working with human cells cultured in a lab, this time around the team tested the process in three mouse models: transgenic mice with HIV-1 DNA in their genome, mice with an acute infection of the mouse equivalent of the virus, and mice carrying human immune cells with a latent HIV infection.

In the first group, the treatment was able to inactivate the virus, reducing its replication by up to 95 percent. It's a similar story for the mice with an acute infection of the equivalent virus (called EcoHIV), with its ability to spread dropping by 96 percent.

"During acute infection, HIV actively replicates," says Dr. Kamel Khalili, co-lead author of the study. "With EcoHIV mice, we were able to investigate the ability of the CRISPR-Cas9 strategy to block viral replication and potentially prevent systemic infection."

For the mice embedded with human cells, just one treatment was enough to remove viral fragments hiding out in the infected human cells. The results hold promise for a possible full HIV cure, but before then, the team needs to conduct more animal trials and eventually, clinical trials in humans.

"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," says Khalili. "Our eventual goal is a clinical trial in human patients."

The research was published in the journal Molecular Therapy.

Source: Temple University