HIV-1 virus DNA was eliminated in the genome of animals, thanks to genomic editing (CRISPR-Cas9) combined with antiretroviral therapy. For this experiment, researchers worked with a mouse model that produces human T cells.
Around the world, around 36 million people are infected with HIV-1. Currently, the therapies used to treat HIV-positive patients prevent the virus from replicating, but does not eliminate it from the body: tri-therapies do not cure HIV and must be continued throughout life. Stopping the anti-retroviral reactivates the virus: it replicates itself again and the disease may evolve into AIDS. This burst is possible because the virus integrates its DNA into the genome of the infected immune cells where it remains dormant in the form of provirus.
Did you know?
Retroviruses, like HIV, have a genome in the form of RNA. With the enzyme reverse transcriptase, the viral RNA is used to make a DNA that integrates into the genome of the infected cell: it is the provirus, which will be transcribed into messenger RNA, to later produce viral proteins.
Antiretrovirals are unable to suppress the provirus of the cell genome. The HIV remains latent in these cells tanks. Only two cases of patients completely cleared the virus have been described in these two particular cases, the patients had transplants of stem cells blood, because of cancer they had developed.
But would it be possible to eliminate the provirus with molecular scissors, such as CRISPR-Cas9? It is on this track that two American teams are working at Temple University and the University of Nebraska. These researchers had already shown that it was possible to eliminate the HIV virus from infected cells in some animal organs, using genomic editing.
Provirus DNA removed from cells in vivo
The originality of this research published in the journal Nature Communications is to have associated genomic editing (CRISPR-Cas9) with antiretrovirals, in this case a therapy called Laser ART, or long-acting slow-effective release antiretroviral therapy (slow-release, long- acting antiretroviral therapy). This medication helps to keep virus replication low and reduce the frequency with which antiretrovirals are administered. The drugs are wrapped in nanocrystals that slowly release the molecules.
Scientists have worked with “humanized” mice that is, modified to produce human T cells, which are the targets of HIV. Once the mice were infected with the virus, they were treated with the antiretroviral laser and then with the CRISPR-Cas9 molecular scissors.
In nearly one-third of the mice (2/7), all of the HIV DNA was deleted in this way. The virus has not been detected in blood, lymphoid tissues, or bone marrow. On the other hand, if researchers used only one of two techniques, antiretrovirals (10 mice) or CRISPR-Cas9 (6 mice), HIV-1 was still detected. Only the combination of both techniques works.
These promising results can be used to imagine new treatments for HIV. The researchers confirm that treatments to suppress HIV replication and genomic editing therapy, when administered sequentially, can eliminate HIV from infected animal cells and organs. We now have a clear path to moving forward with trials on non-human primates and possibly clinical trials on human patients within a year.
What you must remember
- Researchers have been working on mice producing human T lymphocytes.
- They tested two therapies on these HIV-infected mice: genomic editing (CRISPR-Cas9) and antiretrovirals.
- Combining these two techniques has eliminated HIV DNA.