Nearly 40 million people worldwide are living with HIV. Although antiretroviral therapy can suppress the virus to undetectable levels, it cannot completely eliminate it. This is largely due to HIV’s unique ability to persist in a latent state within resting CD4+ T cells, a type of white blood cell. This hidden form of the virus, known as the HIV “reservoir,” has long presented one of the most significant challenges in the quest to find a cure.

Researchers at the Peter Doherty Institute for Infection and Immunity (Doherty Institute), led by a team of Australian scientists, have made a significant breakthrough using the same mRNA technology behind COVID-19 vaccines. In a study published in Nature Communications, the team demonstrated a novel method for delivering mRNA into the HIV reservoir, successfully reactivating the dormant virus.

The research involved packaging mRNA within specially designed lipid nanoparticles—microscopic fat-like bubbles—and transporting them into HIV-infected cells. Once inside, the mRNA prompted the infected cells to expose the latent virus, potentially paving the way for strategies aimed at clearing the virus from the body.

Dr Paula Cevaal, a Research Fellow at the University of Melbourne and co-first author of the study, described the work as a first in HIV research. She explained that the team had designed mRNA to signal infected cells to reveal the hidden virus, but delivering the mRNA to those cells posed a major challenge. The success of the lipid nanoparticles in reaching the target cells and activating the virus represents a promising advance.

According to Dr Cevaal, this is the first time such a strategy has been shown to work so effectively in HIV-infected cells. The team hopes the new nanoparticle design could open up a viable pathway toward an HIV cure.

Laureate Professor Sharon Lewin, Director of the Doherty Institute, co-senior author of the study, and a global leader in HIV cure research, noted that the concept originated from earlier efforts to develop mRNA treatments for COVID-19. That work sparked innovative ideas for tackling HIV, leading to the development of an entire research program focused on using mRNA and lipid nanoparticles to target and eliminate the HIV reservoir. Professor Lewin described the study as a major milestone in this evolving field.

Heather Ellis, HIV advocate and Communications Coordinator at Positive Women Victoria, who has lived with HIV for 30 years, welcomed the findings. While acknowledging that it may take years before such breakthroughs lead to clinical trials and even longer before treatments are widely available, she emphasized the importance of equitable access.

Ellis highlighted the success of antiretroviral treatments since 1996, which allow people with HIV to live long, healthy lives. However, she pointed out that many in developing countries still lack access to these life-saving medications, and expressed hope that any future cure would be scalable and accessible to all. She also noted that a cure could reduce the need for daily medications and help eliminate HIV-related stigma and discrimination.

Dr Michael Roche, Virologist at the Doherty Institute, co-senior author of the study, stated that the team is now preparing for preclinical testing in animal models, with the long-term aim of progressing to human trials. He emphasized that this step is essential for translating the laboratory findings into potential therapies.

Dr Roche also noted that the discovery could have broader implications beyond HIV. The specific white blood cells targeted in this study play roles in various other diseases, including certain cancers and autoimmune conditions. The ability to safely deliver mRNA into these cells could therefore unlock new therapeutic possibilities across a range of illnesses.

Source: https://www.doherty.edu.au/news-events/news/world-first-discovery-harnesses-mrna-in-search-for-hiv-cure