CRISPR / Cas system to be tested intravenously for the first time to treat HIV infection in humans

HIV viruses (green) bud off from an infected lymphocyte

CDC’s Public Health Image Library


The FDA has approved a phase I / II clinical trial for the treatment of HIV infection with intravenous CRISPR / Cas. About it reported on its website, Excision BioTherapeutics, which will conduct the research. In clinical trials, starting at the end of 2021, doctors will evaluate the effectiveness of different dosages of the drug in three groups of HIV-infected volunteers.

The Human Immunodeficiency Virus (HIV) is inserted into the genome of T-lymphocytes because it needs it to reproduce. Once integrated into the chromosome, HIV uses the cell’s RNA polymerase to eventually synthesize virions and spread throughout the body. It is due to the fact that HIV is embedded in the DNA of cells that effective ways to get rid of it have not yet been invented. Described only a few cases of complete deliverance of the patient from HIV due to transplantation of donor red bone marrow cells.

An effective treatment for HIV infection could be CRISPR / Cas technology, which can be used to edit DNA so that the embedded immunodeficiency virus could simply be excised from the genome. Trials of such genetic editing are already carried out on mice. The animals were first given antiretroviral drugs, which helped to weaken HIV, and then tested with the CRISPR / Cas system. Scientists failed to achieve 100% success in treatment: only two out of seven mice completely got rid of traces of HIV DNA.

Research of CRISPR / Cas technology in parallel conducted another team of scientists led by Kamel Khalili of Temple University’s Lewis Katz School of Medicine. They tested the technology on monkey monkeys infected with the monkey immunodeficiency virus. To deliver the construct into animal cells, the scientists used adeno-associated virus 9 (AAV9), which carries information about the endonuclease Cas9, which, using guide RNAs, recognizes the Gag and LTR regions in the viral genome, and then excises these fragments from the cell DNA.

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

The Food and Drug Administration (FDA) has now approved CRISPR / Cas genome editing clinical trials. The technology is similar to that used in experiments on monkeys, but targets the human immunodeficiency virus. Trials of the drug, dubbed EBT-101, will begin in late 2021. Three groups of HIV-infected people will be involved in the research to test different dosages of the drug. Also, doctors plan to develop combinations of CRISPR / Cas therapy and other therapies.

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

This year for the first time experienced intravenous CRISPR / Cas genetic editing. Six patients suffering from transthyretin amyloidosis tolerated the treatment well, and after a month the concentration of transthyretin in their blood decreased by 50-90 percent.

Anastasia Kuznetsova-Fantoni

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