Scientists Successfully Eliminate HIV From The Genomes Of Mice

Current treatment is lifelong and transforms HIV into a chronic, treatable disease that persists throughout the body. Giovanni Cancemi/Shutterstock

In a “groundbreaking discovery”, researchers have successfully eliminated HIV-1 DNA, the virus responsible for AIDS, from the genomes of living animals in what could be a step towards a cure for infection in humans.

It’s estimated that more than 36.9 million people around the world are infected with human immunodeficiency virus type one (HIV-1) and more than 5,000 people become infected every day. Publishing their work in Nature Communications, a multidisciplinary team of scientists describe for the first time the potential for the permanent elimination of the virus.

"Our study shows that treatment to suppress HIV replication and gene editing therapy, when given sequentially, can eliminate HIV from cells and organs of infected animals," said study author Kamel Khalili of Temple University in a statement.

Antiretroviral therapy (ART) is the current treatment for HIV-1. ART suppresses HIV replication but doesn’t eliminate it. Instead, the virus lives within human genomes in “reservoirs” throughout the body. Without ART, HIV can rebound and integrate its DNA into the genomes of immune system cells, lying dormant and out of reach of antiretroviral drugs. It’s not a cure but rather a lifelong treatment, transforming HIV into a chronic, treatable disease that persists throughout the body. Previous studies in rats and mice have shown that gene editing through CRISPR-Cas9 technology is capable of removing HIV DNA from genomes that hold the virus, successfully cutting large fragments of HIV DNA from infected cells and inhibiting viral gene expression. But gene editing can’t eliminate HIV on its own.

In their new treatment method, researchers use a therapeutic antiretroviral method called long-acting slow-effective release (LASER) ART, which strategically targets viral sanctuaries holding HIV and keeps the virus from replicating at high levels over the course of a long period of time. Overall, it reduces the need for ART administration over time. The chemical structure of antiretroviral drugs was modified into nanocrystals that were then distributed to tissues where HIV is likely to be dormant. It’s stored within these cells for weeks at a time, with antiretroviral drugs slowly released. But LASER ART treatment alone isn’t enough. Rather, it suppresses HIV replication long enough for CRISPR-Cas9 to “specifically and efficiently” excise fragments of HIV-1 DNA from the host genome.

It’s certainly a novel concept, but it’s only been done in mice and rats. Researchers engineered mice to produce human T cells that were susceptible to HIV infection. Once infected, the mice were treated with LASER ART and then CRISPR-Cas 9. At the end of their treatment, about one-third of infected mice had seen HIV eliminated from their DNA, specifically 2 of 7 cured in the first experiment, 3 of 6 in the second, and 6 of 10 in the third. It's unclear why specific animals were cleared of the infection and why others weren't. The safety of the approach will need to be tested in order to determine whether it is safe for human use. Regardless, the possibility paves the way for future research and understanding. 

"The big message of this work is that it takes both CRISPR-Cas9 and virus suppression through a method such as LASER ART, administered together, to produce a cure for HIV infection," Dr. Khalili said. "We now have a clear path to move ahead to trials in non-human primates and possibly clinical trials in human patients within the year."

The elimination of HIV-1 infection in humans is documented only in two individuals, both of whom had received stem cell transplants.

A cartoon illustration of the viral elimination strategy is shown for single LASER ART, AAV9-CRISPR-Cas9 injection groups and dual treatment groups. Nature Communications

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