John V. Higginbotham 
The HIV-1 virus DNA was completely removed from the live animal genome, thanks to the combined work of the CRISPR-Cas9 genetic chisel and antiretroviral therapy.
Healing an HIV infection is still impossible to date, because of the ability of the virus to hide in latent reservoirs, cells and tissues in which it manages to camouflage itself despite treatments.
American researchers at the Temple University School of Medicine and the University of Pittsburgh have taken an important step towards complete healing.
They managed to remove HIV-1 DNA from the mouse genomes to eliminate the infection.
Pathologist Wenhui Hu and his colleagues have done so in three different models, including a mouse model that produces human T cells, white blood cells considered to be “elite soldiers” of the immune system.
Landmarks
- Since the advent of HIV / AIDS in the 1980s, more than 30 million people have been swept away by the disease.
- Even today, 36 million people carry the virus.
- If HIV can now be treated, the cure is still out of reach.
- Triple therapy prevents the virus from replicating, but does not eliminate it, so it must be continued for life.
- Stopping antiretrovirals leads to the reactivation of HIV, which is likely to progress to AIDS.
A winning combo
This work is the first to demonstrate that HIV-1 replication can be completely stopped and the virus eliminated from infected cells in animals by the combined action of CRISPR-Cas9 and slow-release antiviral therapy. long-acting (Laser ART).
Our study shows that treatment to suppress HIV replication coupled with gene therapy, when administered sequentially, can eliminate HIV from infected animal cells and organs.
Kamel Khalili, Temple University School of Medicine
Regardless, these two strategies fail to eliminate the virus.
However, their combination shows that Laser ART, by controlling viral replication and reducing the copy number of HIV-1, enhances the ability of CRISPR-Cas9 to eliminate proviral DNA.
The present work is based on a study published by the same team in 2016. It showed at the time that it was possible to eliminate HIV from infected cells in most animal tissues by using Genomics (CRISPR-Cas9).
We have confirmed the data from our previous work and have improved the efficiency of our genetic publishing strategy.
Wenhui Hu, Temple University School of Medicine
“We are also showing that the strategy is effective in two other mouse models, one representing acute infection in mouse cells and the other a chronic or latent infection in human cells,” says Hu.
Encouraging results
Experiments carried out on about twenty “humanized” mice infected with HIV-1 have shown that the virus has been eliminated from the reservoirs in almost one-third of the animals (9/23) treated with both ART and CRISPR- case.9.
We used very advanced detection methods and found no evidence of the virus.
Howard Gendelman, University of Nebraska
Another good news: the CRISPR-Cas9 tool does not cause any collateral damage. Other research has already shown in other contexts that it can sometimes cause involuntary cascade mutations on the rest of the genome.
More work
If researchers are encouraged by their results, they are well aware that they are still far from the announcement of a cure for HIV infection.
Experiments that work in mice do not always work in humans.
Howard Gendelman
The research team has already started testing their protocol in monkeys. If everything goes as she hopes, she could then start a human phase 1 clinical trial as early as 2020, if she gets the green light from the FDA, the US Food and Drug Administration.
The details of this work are published in the journal Nature Communications.
