The technology that powered Covid vaccines may also lead scientists to a cure for H.I.V. Using mRNA, Australian researchers said they were able to trick the virus to come out of hiding, a crucial step in ridding the body of it entirely.
The research, published last week in Nature Communications, is still preliminary, and so far, has been shown to be successful only in a lab. But it suggests that mRNA has potential far beyond its use in vaccines as a means to deliver therapies against stubborn adversaries.
Short for messenger RNA, mRNA is a set of instructions for a gene. In the case of Covid vaccines, the instructions were for a piece of the coronavirus. In the new study, they are for molecules key to targeting H.I.V.
“mRNA is just this miraculous — I really do think miraculous — tool to deliver things that you want into places that were not possible before,” said Dr. Sharon Lewin, director of the Cumming Global Center for Pandemic Therapeutics in Melbourne, who led the study.
Vaccines deploying mRNA instruct the body to produce a fragment of the virus, which then sets off the body’s immune response. In the United States, the shots were initially hailed for turning back the pandemic, then viewed by some with suspicion and fear. Some officials, including Health Secretary Robert F. Kennedy Jr., have falsely said that they are highly dangerous and even deadly.
Last week, the Department of Health and Human Services sought to limit the vaccine’s availability to pregnant women, children and healthy younger adults. The administration also canceled a nearly $600 million contract with the drugmaker Moderna to develop an mRNA shot for humans against bird flu.
“The fear right now is not rational,” Dr. Lewin said. “mRNA vaccines have been given to millions of people around the world, so we have a very good understanding of their risks.”
The new study describes the use of mRNA as a tool to flush H.I.V. out of its hiding places. Other uses could involve providing proteins missing from those with certain diseases or correcting genetic errors.
Frauke Muecksch, a virologist at Heidelberg University in Germany who was not involved in the work, called mRNA a “promising, absolutely powerful technology.”
Although most people may have only heard of mRNA’s use in science during the pandemic, scientists have been working with it for more than 20 years, she said.
“I think it’s not just therapeutically very powerful, but also for basic science, for research, it opens up a lot of avenues,” she added.
Potent antiretroviral drugs can now control H.I.V., suppressing it to undetectable levels. Still, minute amounts of the virus lie dormant in so-called reservoirs, waiting for an opportunity to resurge. A cure for H.I.V. would involve ferreting out all of this virus and destroying it, a strategy that has been called “shock and kill.”
A significant hurdle is that the virus lies dormant in a particular type of immune cell, called a resting CD4 cell. Because these cells are inactive, they tend to be unresponsive to drugs.
The few drugs scientists have previously used to rouse the virus in these cells were not specific to H.I.V. and had unwanted side effects.
“It’s fair to say the field’s been a little bit stuck,” said Brad Jones, a viral immunologist at Weill Cornell Medicine who was not involved in the latest research.
In 2022, Dr. Jones and his colleagues found that the immune boost from the mRNA vaccines wakened latent H.I.V. in people living with the virus. (Other research has shown that mRNA vaccines also activated dormant viruses including Epstein Barr.)
“You get just a little bit of a gentle nudge with some of these vaccines, and it’s enough to coax some of these latent viruses out so they can be killed,” Dr. Jones said.
Dr. Lewin and her colleagues had for years experimented with other ways to activate H.I.V., but had no luck in resting cells. Seeing the success of the Covid vaccines, which used lipid nanoparticles — tiny spheres of fat — containing mRNA, her team tested similar particles.
They used the particles to deliver two different sets of molecules: Tat, which is adept at switching H.I.V. on, and CRISPR, a tool that can “edit” genes.
The researchers showed that in resting immune cells from people living with H.I.V., the approach coaxed the virus out of dormancy.
“It’s very, very hard to deal with these cells, so I think this really targeting the right population of cells is what makes this paper special,” Dr. Muecksch said.
It’s unclear whether the new approach can successfully awaken all of the dormant H.I.V. in the body, and what side effects it might produce.
“mRNA will almost certainly have some adverse effects, as every drug does, but we will investigate that systematically, as we do for any new drug,” Dr. Lewin said. In this case, she said, side effects may be more acceptable to people living with H.I.V. than having to take medications for the rest of their lives.
The researchers plan to test the method in H.I.V.-infected animals next, before moving into clinical trials.
Apoorva Mandavilli reports on science and global health for The Times, with a focus on infectious diseases and pandemics and the public health agencies that try to manage them.
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