World-first discovery harnesses mRNA in the search for an HIV cure

Australian researchers 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.

Nearly 40 million people live with HIV worldwide. While antiretroviral therapy can suppress the virus to undetectable levels, it cannot eliminate it. 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 (Doherty Institute), have discovered a new way to deliver mRNA to the elusive HIV reservoir and coax HIV out of hiding. In a laboratory-based study published in Nature Communications, the team packaged mRNA inside an entirely novel microscopic fat-like bubbles, known as lipid nanoparticles, and successfully transported it into HIV-infected cells, where it prompted the cells to expose the dormant virus.

The University of Melbourne’s Dr Paula Cevaal, Research Fellow at the Doherty Institute and co-first author of the study, said this work is a first in HIV research.

“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 Cevaal.

“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.”

The University of Melbourne’s Laureate Professor Sharon Lewin, Director of the Doherty Institute, co-senior author of the study and a global leader in HIV cure research, said the research provides an important proof-of-concept they 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,” said Professor Lewin.

“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.”

Heather Ellis, HIV advocate, Positive Women Victoria Communications Coordinator and a woman who has been living with HIV for 30 years, said any news about successful HIV cure research is good news, but even though the science looks promising, it is still years before clinical trials and even longer before being available.

“We have had effective HIV treatments since 1996 that control the virus to undetectable levels and allow people with HIV to live long and healthy lives,” said Ms Ellis.

“But there are 40 million people living with HIV globally, of which half are women, and many people with HIV in developing countries don’t have access to these life-saving treatments. I just hope any HIV cure is also scalable so everyone can benefit.

“An HIV cure would also 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.”

The University of Melbourne’s Dr Michael Roche, Virologist at the Doherty Institute and co-senior author, said the team is 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,” said Dr Roche.

“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.”