HIV blood test sample. Credit: Melnikov Dmitriy, Shutterstock
New LNP X nanoparticle delivers mRNA to ‘invisible’ HIV cells without toxicity.
Researchers in Melbourne may have taken a major step toward an HIV cure after discovering a new way to unmask the virus hidden inside human white blood cells. This is something that has long blocked any real progress towards eradication of HIV (Human Immunodeficiency Virus). HIV attacks the body’s immune system and can lead to AIDS (Acquired Immunodeficiency Syndrome) if not treated.
The study, published in Nature Communications in May 2025, describes how scientists from the Peter Doherty Institute for Infection and Immunity developed a new lipid nanoparticle (LNP) called LNP X, capable of delivering mRNA into resting CD4+ T cells, where HIV lies dormant. The mRNA encodes HIV’s Tat protein, which activates viral transcription and essentially “wakes up” the virus.
“To our knowledge, this is the first demonstration of successful, non-toxic in vitro transfection of primary T cells in the absence of T cell pre-stimulation, which was previously thought a pre-requisite for efficient LNP transfection,” the study states.
How using LNP X can expose HIV hiding in the body
HIV hides in a “latent reservoir” within CD4+ T cells, even in people undergoing effective antiretroviral therapy (ART). The LNP X particles encapsulate mRNA coding for the Tat protein, which jumpstarts HIV transcription without triggering unwanted cell activation.
After just one dose of Tat-LNP X, the study found:
- A 112-fold increase in multiply-spliced HIV RNA (Tat-Rev transcripts)
- HIV transcription exceeded that triggered by standard mitogens (PMA/PHA)
- And a 17.2-fold increase in HIV virion production in culture medium.
Importantly, this was done without harming cells or setting off immune alarms.
Researchers are “overwhelmed” by HIV breakthrough
Dr Paula Cevaal, one of the lead authors, told The Guardian the results initially seemed “too good to be true” when they first saw them in the lab.
The new technique significantly outperformed earlier attempts using older nanoparticle designs, which failed to deliver mRNA to the right immune cells.
No cure for HIV yet, but hope remains
Despite the excitement, the scientists were quick to temper expectations.
“In the field of biomedicine, many things eventually don’t make it into the clinic – that is the unfortunate truth,” said Dr Cevaal. “But in terms of specifically the field of HIV cure, we have never seen anything close to as good as what we are seeing.”
No reduction in intact HIV DNA was seen during the study, meaning the virus was not eliminated, just exposed. The next steps would require combining this reactivation with therapies that kill infected cells, something still under development.
The Nature Communications paper concludes that LNP X could be used to deliver mRNA or CRISPR tools to other “hard-to-transfect” cell types such as cancer.
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