Could this strategy mark a turning point in the HIV-cure search?

Worldwide, almost 40 million people live with HIV; and while antiretroviral therapy can suppress the virus to undetectable levels, it cannot eliminate it. In the search for a cure, one of the greatest challenges has been the HIV ‘reservoir’; HIV’s unique ability to hide in a type of white blood cells, resting CD4+ T cells, ready to re-emerge if treatment is stopped. Now, Australian researchers have repurposed the same mRNA delivery system used in COVID-19 vaccines as a potential strategy to find a cure.

“As HIV cure researchers, our goal has been to reach the virus where it hides. We programmed mRNA to tell infected cells to ‘give up’ the virus and make it visible. But getting the mRNA into those cells was the challenge,” said Dr Paula Cevaal from the University of Melbourne, who is a Doherty Institute Research Fellow and one of the researchers on the project. In this laboratory-based study, the team packaged mRNA inside an entirely novel microscopic fat-like bubbles, known as lipid nanoparticles.

The team then successfully transported it into HIV-infected cells, where it prompted the cells to expose the dormant virus. “We were excited to see that a new lipid nanoparticle, essentially a tiny fat bubble, could carry mRNA into HIV-infected cells successfully. It forced the virus out of hiding, which is exactly what we need to start clearing it from the body,” Cevaal said. “This is the first time this strategy has been shown to work in HIV-infected cells. Our hope is that this new nanoparticle design could be a new pathway to an HIV cure.”

According to the University of Melbourne’s Laureate Professor Sharon Lewin, Director of the Doherty Institute and another author on the study, the research provides an important proof-of-concept that the team hope could be a turning point in the field. “Back in 2020, my lab started looking at mRNA to deliver a new treatment for COVID-19. That work sparked a lot of new ideas for HIV, despite the two being very different viruses,” Lewin said.

“Over the last five years, we’ve built this whole new program of work to use mRNA and designed lipid nanoparticles to get to the HIV reservoir and eliminate persistent virus. Our work has changed dramatically and this study is an incredibly exciting milestone,” Lewin added. Also from the University of Melbourne, a Virologist at the Doherty Institute and member of the research team, Dr Michael Roche said they are now preparing for preclinical testing in animal models, with the long-term goal of moving toward human trials.

“Moving into preclinical testing is a crucial next step in translating our findings from the lab to potential therapies,” Roche said. “Importantly, this discovery could have broader implications beyond HIV. The white blood cells where HIV hides are also involved in other diseases, including some cancers and autoimmune conditions. The ability to safely deliver mRNA into these cells opens new possibilities for treating a range of illnesses.”

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‘Efficient mRNA delivery to resting T cells to reverse HIV latency’, has been published open access in Nature Communications and you can read it at doi.org/10.1038/s41467-025-60001-2.

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Image credit: iStock.com/libre de droit