LASER ART against HIV infection
HIV was defeated in mice using CRISPR/Cas and antiretroviral therapy
5 out of 13 mice were cured
Polina Loseva, "The Attic"
American doctors have added the CRISPR/Cas9 system to antiretroviral therapy so that it removes HIV particles from the genome. The new tactic did not give an absolute result, however, 5 out of 13 experimental mice had no traces of infection in the body, and this gives hope that the method can work in humans.
The main way to treat HIV today is antiretroviral therapy. These are substances that block the insertion of the viral genome into the DNA of the cell and its copying. But with the help of antiretroviral drugs, it is impossible to completely expel the virus from the body: individual viral particles persist, begin to multiply after the patient stops taking the drug, and after 2-4 weeks the infection returns. Therefore, HIV-positive people have to take medications for the rest of their lives. The only known cases of cure, which, however, scientists still prefer to call "long–term remission", are the result of a red bone marrow transplant from an HIV-resistant donor. But it is not easy to find a suitable donor for each patient, so the search for a weapon against infection continues.
A group of American researchers proposed a new, two-stage strategy to combat the virus and worked it out on mice. To simulate a human infection, mice were transplanted with human blood stem cells, and then infected with HIV.
At the first stage of treatment, scientists attacked HIV with the help of antiretroviral drugs enclosed in liposomes, that is, fat bubbles. Such balls, on the one hand, can pass through cell membranes (which are also built of fats), and on the other hand, slowly release the medicine outside, which allows you to take it less often. This design was called LASER ART, where ART is "antiretroviral therapy" and LASER is "slow, effective, long–acting release" (long–acting slow effective release).
At the second stage, it was decided to finish off the enemy using the CRISPR/Cas9 system: it was "aimed" at HIV so that it would cut the virus DNA from the genome of cells. The molecular scissors were supposed to eradicate those copies of the virus that managed to integrate into the cellular genome, but could not copy themselves.
The general treatment protocol looked like this: mice were infected with a virus, LASER ART therapy was started two weeks later, it was canceled a month later, CRISPR/Cas9 was introduced three weeks later and the results were analyzed five weeks later.
It turned out that the action of CRISPR/Cas9 itself does not save animals from infection: the amount of viral RNA in the blood practically does not change, and T-lymphocytes (the main victim of the virus) die in the same way as in the control group, which was not treated with anything.
Antiretroviral therapy, as expected, worked well on mice, but caused remission a few weeks after withdrawal. The joint impact of LASER ART and CRISPR/Cas9 helped to keep the number of T-lymphocytes unchanged. In addition, the combination of the drug and genetic editing completely expelled HIV from the body of mice – although only in two of the seven animals in the experimental group. Traces of viral DNA and RNA in these two mice could not be found – neither in the blood itself, nor in blood cells, nor in other organs: the spleen, red bone marrow and intestines. At the same time, scientists also did not find any serious side effects of the action of molecular scissors, that is, DNA cuts in the wrong place.
The researchers also conducted a repeat experiment to check whether it is really possible for animals to completely get rid of HIV, or this can be attributed to measurement errors. Of the six animals treated with the two-stage method, three were finally cured. Neither DNA nor RNA of the virus was found in their bodies either, and even transplanting their blood cells to healthy mice did not infect them with the infection. Thus, scientists have demonstrated that their method can achieve what all other methods of treatment do not allow – the complete expulsion of the virus from the body. True, while the new therapy does not always work, but the researchers call their work "the beginning of a long journey" and expect to achieve more stable results.
Article by Dash et al. Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice is published in the journal Nature Communications, the press release of Gene Editing Strategy Eliminates HIV-1 Infection in Live Animals, Temple Researchers Show can be read on the Temple Health – VM website.
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