New study clears mice of HIV

Is gene editing the long-sought answer to how to effectively eliminate HIV?

The possibilities are growing, according to researchers who have successfully combined gene editing and antiretroviral drugs to treat animals with HIV.

Research published in peer-reviewed journals Proceedings of the National Academy of Sciences (PNAS) said this week that researchers have modified an earlier gene-editing strategy to identify two new genes: HIV-1, the virus that causes AIDS, and a co-receptor that allows the virus to enter cells, called CCR5. describes how to target the

The success of clearing HIV in mice highlights how important CCR5 is in isolating therapeutics and bringing them to humans, the researchers say.

HIV is a deadly virus that attacks the body’s immune system. If left untreated, it can lead to AIDS, a more advanced disease. According to the World Health Organization, more than 40.1 million people have died from HIV.

HIV diagnosis was once a death sentence, but the advent of antiretroviral drugs as a treatment has enabled HIV-infected people to live without fear of progressing the disease or infecting others.

But scientists are still looking for an actual cure.

Howard E. Gendelman, Professor of Pharmacology and Empirical Neuroscience at the University of Nebraska Medical Center (UNMC) said: said in a press release. “Through our ongoing collaboration, Temple and UNMC have conducted meaningful research that could ultimately impact the lives of many.”

Gendelman is one of the authors behind this new study. For years, he has partnered with a team led by Kamel Hariri, professor and director of the Comprehensive NeuroAIDS Center at Temple University’s Lewis Katz School of Medicine, to combine individual HIV research into his HIV Seeking better treatments.

This new research is the latest step in the collaboration.

Gendelman’s team is developing a technology called LASER-ART, which stands for “long-acting, sustained-release antiretroviral therapy,” which could allow for less frequent antiretroviral therapy to fight HIV. I am working on the development. Khalili’s team focuses on CRISPR gene editing technology.

CRISPR gene editing works by precisely breaking a DNA strand and allowing natural DNA processes to take over and repair the break. This strategy means that specific sections of DNA can be removed, added or altered with high specificity. This is important when dealing with the highly complex components of living organisms.

Previously, the two teams had established that HIV could be edited from the genome of living humanized HIV-infected mice by combining LASER-ART and CRISPR gene-editing techniques. When an animal is “humanized”, it is the use of human her DNA or tissues, such as tumors, to better study treatments and interventions for human problems within animal models prior to human clinical trials. It means that a small part is ported.

In this previous study, first revealed in 2019, researchers were able to cure some mice. It meant that I didn’t know if it was a fluke or not.

Another problem is that despite the ability to eliminate HIV in mouse tissue, HIV is similar to that seen in humans who have been on regular antiretroviral therapy but who subsequently discontinue treatment experience rebound infection. is likely to reappear, researchers have found.

To find ways to stop rebound infections, researchers turned to a few isolated cases of HIV being cleared from humans.

A renewed focus was then placed on the receptor CCR5.

“The idea of ​​using gene-editing techniques to combine HIV-1 DNA ablation with CCR5 inactivation is based on observations from reported cures in human HIV patients,” said Khalili. .

“In one of the few examples of HIV cure in humans, a patient underwent a bone marrow transplant for leukemia and the donor cells used had an inactivating CCR5 mutation.”

In hopes of permanently removing the virus, researchers decided to modify the CRISPR technology in combination with laser art to target both the virus and the receptor at the same time.

“Our hypothesis was that loss of the viral receptor, CCR5, is critical to permanently eliminate HIV infection,” Khalili explained in the release.

They found that they were able to suppress the virus, restore human T cells, and eliminate HIV-1 replication in more than half of the mice using this strategy.

This is a much larger proportion of mouse samples compared to previous attempts to eliminate HIV in mice. According to the researchers, these findings strongly support the theory that CCR5 is a key domain for eradicating HIV.

“We are true partners and what we have achieved here is truly amazing,” said Gendelman in the release. “Dr. Khalili’s team generated the essential gene-editing constructs and applied these constructs to the Nebraska laser art mouse model to determine when to administer gene-editing therapy, to ablate HIV-1, CCR5 inactivation and inhibits viral proliferation.”

They believe that this dual CRISPR gene-editing strategy, which focuses on these two targets simultaneously, could be highly successful in humans when refined.

And given the small number of previously seen human treatments requiring intensive care reserved for leukemia, this would be much more accessible.

“It’s a simple and relatively inexpensive approach,” says Kariri. “The type of bone marrow transplant that has provided a cure for humans is reserved for leukemia patients. not applicable.”

The next step for researchers is to test dual gene-editing strategies in non-human primates. If it works, human trials could be imminent.