Scientists Use mRNA Nanoparticles to Force Hidden HIV Out of White Blood Cells

A complete cure for HIV has long been blocked by one frustrating reality: the virus hides. Even in patients on lifelong antiretroviral therapy, HIV burrows into resting CD4+ T cells—white blood cells that quietly carry the virus in a dormant state, untouched by drugs or immune responses.

Now, scientists at the Peter Doherty Institute in Melbourne have achieved something that was previously thought impossible: they’ve used mRNA-loaded lipid nanoparticles to enter those elusive cells and force the dormant virus into the open. The technique, described in a June 2025 paper published in Nature Communications, may mark a major turning point in the decades-long effort to cure HIV.

LNP X, the new delivery system developed by the researchers, builds on lipid nanoparticle technology used in COVID-19 vaccines but with a crucial upgrade. Unlike earlier formulations, this version is able to enter resting CD4+ T cells—an especially challenging target—and deliver mRNA without triggering cell activation or causing harm.

Once inside, the mRNA instructs the cells to produce HIV’s Tat protein—a viral activator that wakes the virus up, making it visible to the immune system or future treatments.

A Hidden Target, Now Within Reach

Until now, delivering anything into resting T cells was nearly impossible. These cells are designed to stay quiet and resist manipulation. Traditional nanoparticles were simply ignored. But LNP X changes the game.

In lab experiments using blood samples from people living with HIV, the LNP X-mRNA package triggered a measurable increase in HIV gene activity. Dormant virus, once undetectable, was reactivated inside the cells. That doesn’t eliminate HIV from the body—but it makes it visible, which is the first essential step toward destroying it.

Dr. Paula Cevaal, co-lead author of the study, explained that they repeated the tests multiple times, and each time the results were consistent and significantly better than anything they had previously observed.

The research also shows that LNP X can carry more than just Tat. It successfully delivered CRISPR-based gene activators as well, opening the door to future strategies that fine-tune both viral and host cell behavior.

Why This Matters

For over a decade, scientists have floated the idea of a “shock and kill” strategy—activate latent HIV and then destroy the infected cells. But the “shock” part has always been unreliable. LNP X could be the first tool that delivers this activation step with precision and efficiency.

The technology is still in its early stages. The current results are limited to cell samples tested in a lab. Scientists will need to develop strategies to actually kill the infected cells afterward.

Researchers, including co-senior author Dr. Michael Roche, believe the platform could have broader applications beyond HIV. He noted that resting CD4+ T cells play roles in various conditions such as cancer, autoimmune diseases, and immune suppression. If these cells can now be targeted with mRNA or CRISPR-based therapies, it could open the door to a wide range of new treatment possibilities.

Even a small fraction—such as 10%—could potentially be enough to reignite the infection. Despite this uncertainty, he acknowledged that the findings represent a major step forward.

There is no silver bullet for HIV. But this breakthrough—delivering mRNA directly into the virus’s safest hiding place—may finally remove one of the biggest obstacles to a cure. With further development, the approach could transform how we treat not just HIV, but other diseases tied to immune cell behavior.

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