Researchers from the Lewis Katz School of Medicine in Temple University have used gene editing technology in order to remove a segment of HIV-1 from the genomes of animals. The findings were published online in Gene Therapy journal and are a crucial step towards a cure for HIV.
Lead investigator on the study, Kamel Khalili said he and his team have shown that their gene editing technology can be used on many organs, cutting out large fragments of viral DNA from the host cell genome. Currently, HIV is treated via a combination of antiretroviral drugs which are not able to eliminate HIV-1 from infected cells but can limit the spread of the virus. If at any point, the treated is paused or halted, the virus starts spreading rapidly and puts patients at risk of getting AIDS.
Dr. Khalili and his team have previously shown in their research that their gene editing system (which was based on CRISPR/Cas9 technology) is able to completely remove HIV-1 from infected cells in vitro with absolutely zero side effects. During clinical specimen testing, T-cells were used from patients infected with HIV and viral replication was greatly lowered upon treatment.
The latest tests focused on using the gene editing technology in transgenic rats and mice. The goal was to see if HIV-1 could be eliminated when HIV DNA was present in the genome of every single cell and organ. A recombinant adeno-associated viral vector delivery system (rAAV) was used that was engineered to sever the HIV-1 DNA within the host cell genome.
Two weeks after the rAAV CRISPR/Cas-9 molecules were sent into the bloodstream, tissue DNA showed that the targeted area of HIV-1 DNA had been completely removed from the viral genome in every single tissue throughout the body (the brain, kidney, liver, spleen, blood, etc). There was also a significant drop in HIV-1 RNA in lymphocytes and lymph nodes.
Dr. Khalili says the ability of the rAAV delivery system to go inside organs that have the HIV-1 genome and edit the body’s viral DNA is a very good sign that this strategy will be able to overcome viral reactivation from latently infected cells and holds the potential to one day lead to a cure for those suffering with HIV. By excising the HIV-1 DNA, there is no chance of replication or escape for the virus.
Not only may this strategy one day be able to bring a cure to sufferers of HIV, but it could be used in combination with existing drug treatments t hat suppress viral RNA and to target mutated HIV strains. Clinical trials may take a few years to complete, but researchers are also working on a new study that will use a larger number of animals. Focus will be placed on effects of treatment and overall safety before human trials will be considered.