mRNA used to force HIV out of hiding

Australian researchers say they have made a major breakthrough in HIV research by repurposing the same mRNA delivery system used in COVID-19 vaccines — not to prevent infection, but as a potential strategy to find a cure.

While antiretroviral therapy can suppress HIV to undetectable levels, it cannot eliminate it. This is because HIV has a unique ability to hide in a type of white blood cells, resting CD4⁺ T cells, ready to re-emerge if treatment is stopped. This HIV ‘reservoir’ has long been one of the greatest challenges in the search for a cure.

Using the same technology behind mRNA COVID-19 vaccines, researchers led by The Peter Doherty Institute for Infection and Immunity have discovered a way to deliver mRNA to the elusive HIV reservoir and coax HIV out of hiding. In a laboratory-based study published in the journal Nature Communications, the team packaged mRNA inside a novel lipid nanoparticle and successfully transported it into HIV-infected cells, where it prompted the cells to expose the dormant virus.

“As HIV cure researchers, our goal has been to reach the virus where it hides,” explained Dr Paula Cevaal, a research fellow at the Doherty Institute and co-first author on the study. “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.

“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.

“This is the first time this strategy has been shown to work so well in HIV-infected cells. Our hope is that this new nanoparticle design could be a new pathway to an HIV cure.”

Doherty Institute Director Professor Sharon Lewin, who is co-senior author on the study and a global leader in HIV cure research, said the research provides an important proof of concept that 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,” Lewin said. “That work sparked a lot of new ideas for HIV, despite the two being very different viruses.

“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.”

HIV advocate Heather Ellis, who has been living with the virus for 30 years, said any news about a potential HIV cure is good news, although it will be years before clinical trials can commence and even longer before a cure will be available.

“An HIV cure would … mean we don’t have to take daily pills, which for some present side effects, and hopefully would mean we don’t have to face HIV-related stigma and discrimination,” Ellis said.

“I just hope any HIV cure is also scalable so everyone can benefit.”

Co-senior author Dr Michael Roche, a virologist at the Doherty Institute, said the team is now preparing for preclinical testing in animal models, with the long-term goal of moving toward human trials.

“Importantly, this discovery could have broader implications beyond HIV,” he noted. “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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