HIV treatment with CRISPR may soon be available
Antiretroviral (ARV) drugs are the method used against the HIV virus. With this treatment method, the virus turned from being deadly to being chronic. In about 10 percent of infected people, HIV is easily detected in the blood, even if they take their daily medication and do not carry out drug-resistant mutants of the virus.
A study presented at the United States’ largest annual HIV/AIDS conference offered a solution to this conundrum; CRISPR therapy.
The Crispr treatment deletes any genetic code from the cell, preventing the virus from replicating itself in that cell. This method has been tried on mice before and has been successful.
These replicas also highlight what may be a serious shortcoming in a popular HIV treatment strategy. They are drawing new attention to a radical approach to eradicate the persistent virus; They use the CRISPR genome method to get the genes of HIV out of infected cells. The monkey study of the approach presented at the same meeting showed signs of success, and a biotech company is now considering launching a clinical trial.
John Mellors, a virologist at the University of Pittsburgh in Pennsylvania, said that some patients still have little virus in their blood despite using ARVs. Mellors attributes this to the virus gaining resistance. Stating that patients who have become resistant to the virus take new supplements by frequently changing their drug regimens, the expert said, “Each of these causes anxiety and creates new side effects. What’s more, these people may have enough viral loads to infect others.” says.
At the conference, virologist Elias Halvas, who works in Mellors’ lab, explained that he carefully analyzed viral isolation and blood cells from eight men and one woman who had mysterious, persistent low-level viremia despite using ARVs for an average of 3 years. Halvas and his team realized something; Normally, each time HIV infects a cell, the virus copies its RNA genome into a version of DNA that integrates at a new point between the cell’s chromosomes. In each of these patients, however, HIV was integrated into the same chromosomal region in all of their infected cells. The sequence of HIV DNA from different cells in the same person was also the same.
Researchers have long known that HIV can make new copies in two ways. In the basic replication cycle, HIV DNA in a chromosome creates new virions that budding in that cell, then infecting other cells, each time receiving mutations. ARVs block multiple steps in this process.
In the second route, HIV essentially enters the free circulation. Because it infects an immune cell that clones itself, making more cells that carry the viral genome. ARVs have no effect on this scenario. Viral DNA ends at the same chromosomal location in all progeny cells without acquiring any new mutations. These clones may themselves produce new virions, but ARVs ingested by patients derail new infections.
CRISPR is not safe at the moment
“It may one day be possible to remove persistent HIV DNA from a person’s chromosomes with CRISPR genome therapy.” says the scientist Pavlakis. But now, he claims, the risks are too high, as CRISPR cuts the Cas9 enzyme in the wrong place and the method redirects to the appropriate cells.
At the meeting, Temple University neurovirologist Tricia Burdo explained the first step: “We removed at least some of the AIDS virus in monkeys from the chromosomes of the two monkeys.” Previous studies had shown that CRISPR destroyed HIV implanted in mice cells. In the new study, researchers infected an adeno-associated virus that damaged the vessels of two SIV-infected monkeys that carried the genes for the molecular scissors targeted by CRISPR. Monkeys used ARVs and had low SIV levels.
After mice, it also worked for monkeys
Necropsies of the treated animals showed that CRISPR cut the SIV DNA. The group also found Cas9 in all 14 edited tissues, indicating that the study virus had spread throughout the body as intended. “The data show much stronger effects than seen before, so we think it’s a step in the right direction,” said John Coffin, a retrovirologist at Tufts University in Boston. He said he supports the work.
The researchers say they won’t be giving ARVs to CRISPR-treated monkeys in the future to see if the virus will reactivate. They also plan to transfer millions of blood cells from monkeys treated with CRISPR to infected animals.
Temple University neurovirologist Kamel Khalili is considering developing a human version of this CRISPR gene therapy. Khalili said Philadelphia-based Excision BioTherapeutics is seeking approval to launch CRISPR excision trials in humans by the end of this year.