Though advances in medicine have greatly improved the lives of HIV sufferers and made the virus much more manageable, a permanent cure has remained elusive. Scientists have now made a significant breakthrough in this area, using the CRISPR-Cas9 gene editing tool to entirely remove the virus from the genomes of living animals for the first time ever.
Part of the reason HIV has been so difficult to cure is because when it's not busy replicating and spreading around the body, it can lay dormant and remain invisible to its host's immune system. Once those immune defenses are out of sight, it can come out of the woodwork and begin replicating and infecting again with wild abandon.
Current day antiretroviral drugs are good at keeping these crafty machinations in check to stave off attacks and help prevent transmission. But it goes without saying that to rid the body of the virus once and for all would be a far better outcome, and lately we are seeing some exciting progress toward this goal.
At the cutting edge of these advances are the researchers at Temple University's School of Medicine, who in 2014 figured out how to use gene editing to permanently eliminate the HIV virus from cultured human cells. They have now turned this type of technology to the genomes of living animals, and working with scientists at the University of Nebraska Medical Center, have produced some exciting results.
The researchers have been pursuing a permanent cure for HIV through the CRISPR-Cas9 tool, a gene editing technology that can be used to snip certain sequences out of an organism's DNA. HIV's replication strategy is based on its ability to infiltrate immune cells with its own DNA sequence, so in some ways it presents as a perfect potential use case for the gene-editing technology.
The breakthrough stems from the combination of CRISPR-Cas9 with a new kind of antiretroviral therapy (ART) called LASER ART, which allows antiretroviral drugs to be slowly released over weeks, keeping HIV replication low for longer periods of time. The researchers wanted to find out if it could dampen the HIV replication for long enough for CRISPR-Cas9 to get rid of it entirely.
They investigated this theory in mice engineered to be vulnerable HIV infection. They then treated the mice with LASER ART to reduce the virus to very low levels, and used CRISPR-Cas9 to then cut away the relevant DNA sequences from within the infected cells. Follow-up analysis revealed that HIV had been completely eliminated in around a third of the mice.
"The big message of this work is that it takes both CRISPR-Cas9 and virus suppression through a method such as LASER ART, administered together, to produce a cure for HIV infection," Dr. Khalili says. "We now have a clear path to move ahead to trials in non-human primates and possibly clinical trials in human patients within the year."
The research was published in the journal Nature Communications.
Source: Temple University via MedicalXpress
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