Elimination of HIV from Genome Could Potentially Lead to Cure

Approximately 36.7 million people are infected with HIV around the world and more than 5,000 are infected each day. Where available, the disease is largely controllable through antiretroviral therapy (ART), but ART doesn’t actually eradicate copies of the HIV-1 proviral DNA from the genomes of infected cells. This means that if ART is ended, the HIV infection can come back and progress to AIDS.

Researchers at the Lewis Katz School of Medicine at Temple University and the University of Nebraska Medical Center (UNMC) have developed a technique that is capable of eliminating replication-competent HIV-1 DNA from the genomes of living animals. They published their research in the journal Nature Communications. Excision BioTherapeutics holds the license for commercial application of the technology.

The technology uses CRISPR-Cas9 gene editing and a long-acting slow-effective release (LASER) ART, which was co-developed by Howard Gendelman and Benson Edagwa. LASER ART places HIV antiretroviral drugs into nanocrystals. This decreases the need for ART administration and allows, in animal studies at least, more effective HIV treatment. Gendelman is the Chair of the Department of Pharmacology and Experimental Neuroscience at UNMC. Edagwa is an assistant professor of Pharmacology at UNMC.

“The results further validate the efforts of Excision to take the product forward to patients and it’s one of the primary reasons I became a founding member of the company,” stated Kamel Khalili, Professor and Chair of Neuroscience at Lewis Katz School of Medicine and founder and Principal Scientific Advisor to Excision. “The next step is to bring this from the bench to the clinic, and to make this life-changing development commercially available.”

In an interview with NET News, Nebraska’s PBS and NPR stations, Gendelman said, “What we’ve done is to transform the anti-retroviral drugs from a water-soluble, short half-life medicine to a nanocrystal and encased it into a nanoformulation that can be given infrequently and is long-lasting over a period of months up to as long as a year. These nanocrystals can reach lymphoid tissues, like the lymph nodes, the spleen and the gut, as well as the brain, in very high concentrations over long periods of time.”

So far, the technique has been successful in animal models that mirror the human infection, using human cells in the animals. Before being fully tested in humans, they will test it in other species using animal models that are more similar to the human HIV infection.

Asked how close this brings us to a cure for HIV, Gendelman told NET News, “There’s still a lot more research to be done. But what I can say is this research does provide proof of concept. It does tell us what we have it in our power to eliminate HIV from an infected animal, infected person. The technology exists.”

Excision BioTherapeutics hopes to enter the technology into clinical trials.

“We are incredibly proud of the medical breakthroughs made by this team of scientists,” stated Daniel Dornbusch, chief executive officer of Excision. “As the exclusive license holders from Temple on the technology and patents behind these innovations, Excision is working closely with the team to bring these advances to human clinical trials and to patients in need around the world.”