Researchers snip HIV from infected cells, suggesting a cure is possible

PHILADELPHIA » Temple University researchers used a gene-editing technique to remove HIV DNA from the type of human immune cells where the virus maintains a smoldering reservoir of infection.

The experiment, building on the researchers’ previous HIV gene-editing work, was conducted in T cells growing in lab dishes. Whether it works in actual patients remains to be seen.

Still, the study bolsters the concept that HIV, the virus that causes AIDS, can be cured, not just controlled in a latent stage by antiviral drugs.

Achieving a cure has been a bedeviling challenge because there has been no way to eliminate latent viral DNA from an infected cell’s genetic code without destroying that cell.

“We might be able someday to cure HIV right here in Philadelphia,” said Temple neurovirologist Kamel Khalili, leader of the study published online this month in the journal Scientific Reports.

A more reserved view was offered by Manjunath N. Swamy, an infectious disease specialist who has used gene-editing in HIV research at Texas Tech University Health Sciences Center in El Paso.

Swamy pointed out that when patients take anti-HIV drugs, viral replication is so suppressed that only about one immune T cell in a million has a latent infection. Gene-editing “these rare cells is a major hurdle, precluding its clinical use anytime soon,” he said.

The gene-editing technology, called CRISPR, is barely five years old and has not yet been used in patients. Even so, it is seen as a potentially revolutionary medical tool. It combines a synthetic “guide RNA” — a genetic version of the search function in a word processor — with an enzyme that acts like molecular scissors.

For a study published in 2014, the Temple researchers used CRISPR to eradicate latent HIV primarily from certain immune cells that harbor the virus in the brain. They also showed that the guide RNA and scissor enzyme persisted in the cleared cells, thus preventing reinfection by HIV.

The new study focused on “T helper cells,” which assist and signal other immune cells. HIV hides out in these cells, then uses them to replicate, destroying them in the process.

In up to 90 percent of latently infected T cells, CRISPR eliminated the HIV DNA and prevented reinfection. What’s more, the researchers found no evidence that unintended segments of genetic material were cut, a potential problem that could have toxic effects.

In addition to using CRISPR on cell colonies developed for lab experiments, Khalili’s team used the gene-editing method on T cells obtained from the blood of HIV-infected patients. Again, it dramatically reduced latent virus.

Khalili said his team will soon publish results of gene editing experiments in a rodent model of HIV infection. They are also “moving forward” with efforts to get regulatory permission and funding for human testing, he said.

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