New gene editing method eliminates HIV infection in mice

New research by several US institutions found that gene editing therapy can effectively eliminate human immunodeficiency virus (HIV) infection. It has been the first to combine a dual strategy of editing genes necessary for infection with the HIV-1 virus, which causes AIDS, with antiretroviral drugs to completely cure said infection.

«The idea of ​​combining the cleavage of HIV-1 DNA with the inactivation of CCR5 [el correceptor que ayuda al virus a ingresar a las células] using gene editing technology is based on observations of reported cures in human patients with HIV,” explained Kamel Khalili, professor at Temple University School of Medicine. “In the few cases of human HIV cures, patients underwent a bone marrow transplant for leukemia and the donor cells used carried inactivating CCR5 mutations.”

In previous studies, researchers were able to eliminate HIV in a line of humanized mice (which carry functional human genes, cells, tissues and/or organs and are commonly used as models in biological and medical research for human therapeutics) using an approach therapeutic known as ‘LASER-ART’. This strategy is based on applying antiretroviral therapy (ART) through its slow and effective release with prolonged action (LASER). LASER-ART keeps HIV replication at low levels for long periods of time and was co-developed by Howard E. Gendelman and Benson Edagwa of the University of Nebraska Medical Center.

However, the researchers found that HIV could eventually re-emerge from tissue reservoirs where it is beyond the reach of antiretrovirals and cause rebound infection. It does this because HIV integrates its DNA into the genome of the host cells for long periods of time, until antiretroviral therapy stops and relapse occurs.

A strategic cooperation

The strategic combination of CRISPR gene editing technology to produce inactivating mutations in the leukocyte receptor CCR5 and the HIV-1LTR-Gag viral DNA, with the LASER ART approach, allowed permanent elimination of the virus. Experiments with humanized mice resulted in viral suppression, restoration of human T cells, and elimination of HIV-1 replication in 58% of infected animals. The study was published this Monday in the scientific journal PNAS.

The novel dual gene editing strategy CRISPR holds exceptional promise for the treatment of HIV in humans. “It’s a simple and relatively inexpensive approach,” Khalili said. The research team plans to soon test the dual gene editing strategy in primates to advance its implementation in sick people. With RT

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