CRISPR/Cas against HIV infection

The CRISPR/Cas system will be tested intravenously for the first time for the treatment of HIV infection in humans

Anastasia Kuznetsova-Fantoni, N+1

The FDA has approved phase I/II clinical trials of HIV infection therapy using intravenous CRISPR/Cas. This was reported on Excision BioTherapeutics company, which will conduct research on its website.

The human immunodeficiency virus (HIV) is embedded in the genome of T-lymphocytes, because it needs it for reproduction. Once integrated into the chromosome, HIV uses the cell's RNA polymerase to eventually synthesize virions and spread throughout the body. Precisely because HIV is embedded in The DNA of cells has not yet been invented effective ways to get rid of it. Only isolated cases of a patient completely getting rid of HIV due to the transplantation of donor red bone marrow cells have been described.

An effective method of treating HIV infection could be CRISPR/Cas technology, with which DNA can be edited, so that the built-in immunodeficiency virus could simply be cut from the genome. Tests of such genetic editing have already been carried out on mice. The animals were first injected with antiretroviral drugs that helped to weaken HIV, and then the CRISPR/Cas system was tested. Scientists failed to achieve absolute success in treatment: only two out of seven mice completely got rid of traces of HIV DNA.

CRISPR/Cas technology research was conducted in parallel by another team of scientists led by Kamel Khalili from the Lewis Katz School of Medicine at Temple University. They tested the technology on macaques infected with the monkey immunodeficiency virus. To deliver the construct to animal cells, scientists used the adeno-associated virus 9 (AAV9), which carries information about the Cas9 endonuclease, which, using guide RNAs, recognizes the Gag (key HIV gene) and LTR (terminal fragments) regions in the viral genome, and then cuts these fragments from the DNA of cells.

First, the monkeys were given a course of antiretroviral therapy, and then intravenously injected with CRISPR /Cas. Scientists have not been able to completely rid lymph node cells of HIV (the amount of viral DNA decreased by 38-95 percent), but the technology has shown its potential.

Now the FDA has approved clinical trials of genomic editing using CRISPR/Cas. The technology is similar to the one used in experiments on monkeys, but is aimed at the human immunodeficiency virus. Trials of the drug, which was named EBT-101, will begin at the end of 2021. Three groups of HIV-infected people will be involved in the research to test different dosages of the drug. Doctors also plan to develop combinations of CRISPR/Cas therapy and other treatment methods.

It is too early to talk about a breakthrough in the treatment of HIV infection, as scientists have yet to prove not only the effectiveness of treatment with the CRISPR/Cas system, but also its safety. Side effects from the use of EBT-101 will be evaluated by physicians in phase I/II clinical trials.

This year, for the first time, genetic editing using CRISPR/Cas was tested intravenously. Six patients suffering from transtyretin amyloidosis underwent treatment well, and after a month, the concentrations of transtyretin in their blood decreased by 50-90 percent.

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