Temple University researchers have used state-of-the-art molecular scissors to cut out dormant HIV hiding in human cells, fueling hopes for curing - not just suppressing - the insidious infection that causes AIDS.
The HIV removal experiment was conducted in cells in the lab, and the scissors did not work on every cell, so the approach is a long way from use in the clinic.
Still, the study, published Monday in Proceedings of the National Academy of Sciences, shows how new genetic editing technologies could be harnessed to conquer the AIDS virus.
"There is no demonstration yet that it has worked in a person, so caution is appropriate," said Clyde Crumpacker, an AIDS researcher with Beth Israel Deaconess Medical Center at Harvard Medical School. "But it is a very intriguing paper about a possible strategy for an HIV cure. This is a timely 'proof of concept' paper."
The need for such strategies has never been greater, as evidenced by the 14,000 scientists and activists from 200 countries now gathered in Melbourne, Australia, for the annual International AIDS Conference.
Although antiviral medications that block HIV replication have turned it into a manageable disease, the lifelong drug regimen has limitations. Cost is a barrier in developing countries, where most of the world's 35 million HIV/AIDS patients live. And the virus remains tucked in the patient's own DNA, where it causes low-level damage to many organs - and threatens to resurge if drug therapy is stopped.
Therapy "doesn't completely suppress viral gene [activity] - and some of those viral proteins are basically toxic," said Temple University neurovirologist Kamel Khalili, who led the new study.
Khalili's team used a new gene editing technology, called CRISPR, that combines a "guide RNA" - a genetic version of the search function in a word processor - with an enzyme that acts like scissors.
A few labs have already shown that CRISPR can be used to hunt down and disrupt latent HIV. Last summer, for example, researchers at Kyoto University in Japan published a study in which they deleted parts of HIV's genetic code from human cells grown in the lab.
The Temple team managed to improve the efficiency and effectiveness of this strategy by precisely identifying the attachment sites at the ends of the viral DNA, then creating guide RNA that zeroed in on these sites.
"We were able to remove everything which encodes the virus - close to 99 percent of the HIV genome," said Khalili. "What is left has no capacity to do anything. It's just junk DNA."
This HIV eradication was highly effective in three types of immune system cells that the virus uses to build a reservoir in the brain and blood.
Khalili's team also showed that by introducing the guide RNA and scissor enzyme into healthy cells, they could prevent HIV from infecting the cells - in other words, the editing system also acted like a vaccine.
"These properties may provide a viable path toward a permanent cure for AIDS, and provide a means to vaccinate against other pathogenic viruses," the researchers wrote.
N. Manjunath, who recently wrote about the promise of gene editing technologies in HIV therapy, was more guarded in his assessment.
"This paper is good, but it's only an incremental step over what's already been done, and it is not easy to get [gene editing] into humans," said Manjunath, an infectious disease specialist at Texas Tech University Health Sciences Center in El Paso. "The potential is there, but there are a lot of hurdles to get this into the clinic."
Toward that end, Khalili's lab is now planning studies using the technology in an animal model.
"We have a long way to go, but what we have done is something that has not been done before," the Temple researcher said. "We showed that this system is capable of basically doing a sterilizing cure in cell culture."