Scientists have worked in a quest of curing HIV more than 40 years. Although there is therapy available to prevent the virus such as antiretroviral therapy (ART), this does not eradicate the virus. Today, there is a new scientific discovery with a promise of an actual cure thyroid disease-based on the same technology used to develop the COVID-19 vaccines.
In an upcoming paper in Nature Communications (2025) a team of researchers at the University of Melbourne has demonstrated a potent strategy to reactivate latent HIV by injecting microscopic packages of mRNA into immune cells. The lipid nanoparticle (LNP) wrapping protects these packages so that they can be delivered safely within the cells of the body with the help of these lipid nanoparticles as the protective measure due to their tubular nature that resembles the tube of lipids which can be understood as a closed fat bubble.
The Issue: HIV Hiding in Body
When one becomes infected with HIV, the virus engages in concealment within the cells of the immune system, particularly the CD4+ T cells. The virus is hiding just like a criminal in a clandestine base though, the viral levels are getting too low to a point where it is not detectable anymore even though the person takes drugs on a daily basis (ART). This is termed as HIV latency.
All these lurking viruses may, at any time, come out of hibernation once the treatment is halted enabling the virus to remerge rapidly. This is the reason why HIV-positive individuals have to have the ART treatment on a daily basis throughout their lives.
Scientists have tried to seek a means to clear the lurking virus. This concept is dubbed as the kick and kill concept, wake the sleeping virus and then kill the infected cells before the virus can reach its full potential. However, majority of the approaches have either been weak or have triggered undesirable collateral effects such as stimulation of the entire immune system.
The Breakthrough: aling HIV with mRNA
Researchers are finding ways of using the same mRNA technology found in Pfizer and Moderna COVID-19 vaccines to combat HIV.
The researchers designed a different LNP formulation, namely, LNP X, which can directly enter resting (not active) CD4+ T cells the cells into which HIV hides, in this new study. That is a big thing, as these resting cells are normally extremely tough to access using medicine.
The team has packaged mRNA which directs the cells to produce HIV Tat, which is a protein that naturally stimulates the virus to start copying itself. When LNP X delivered the Tat protein into the hiding cells something extraordinary occurred, the virus woke up.
The researchers observed a huge rise in HIV action inside the cells and it did not cause any inflammation or damage to the cells. That implied that the virus was washing through and its response was not triggering a potentially harmful immune response.
What was its strength?
As compared to the age-old methods, this new Tat-LNP X was:
112 times more effective at turning on the essential HIV gene
Better than even the most potent chemicals found in a lab should be to rouse HIV
Non-toxic, not harmful to the immune cells and did not cause stress in the cell
Who will be even more exciting? These findings were performed in the cells of actual individuals living with HIV and on ART, not only in a model in the laboratory.
Nevertheless, Tat-LNP X was able to activate the virus but it could not kill an infected cell on its own. This implies that it might require that other therapies be added, which aids the immune system to identify and kill those cells.
The CRISPR Twist
The group also tried another futuristic technology: CRISPRa, a gene-editing technology meant to activate genes rather than snip DNA.
They applied it to the same resting T cells and injecting them with LNP X to deliver CRISPRa. It did the trick – The CRISPRa awakened the HIV genes precisely in the same fashion as Tat, however, more specifically. It was weaker in power, quite narrow and non-hazardous.
This holds the potential of gene targeted treatment of HIV in the future, without the introduction of viruses or electric shock to enter the cells.
So what is Different?
Past ways involved small chemicals that would result in lots of side effects and would not work so well. This new way of doing it is:
Attacks the HIV infected cells only
Incorporates mRNA that does not get incorporated in the DNA and does not make a permanent change
Does not stimulate the entire immune system
Possibly, one time able to be injected as a vaccine
And the most wonderful thing? It is where the same LNP method can be applied to other treatments as well, such as cancer immunotherapy, autoimmune disease or even other viruses.
Is this a Cure then?
Yet not but a big step in the right direction.
The new approach aids researchers to accomplish one of the most difficult aspects of HIV curing locating and activating sleeping virus. Then will come the trick of how to get rid of or kill those reactivated cells safely. Scientists can couple this approach with immune enhancers or so called kill switches that induced infected cells to self-liquidate.
It should be tested a bit more before it gets available:
Safety experiments and research in animals
Becoming familiar with the duration of the impact
Human studies Large testing
However, in case all goes well, such a procedure might lead to the fact that people with HIV could stop taking pills every day and remained free of the virus.
Brighter Day Ahead
The discovery paves the way to the strength of mRNA and nanotechnology beyond the COVID-19 vaccines. Researchers are only learning how to apply it to their sensitive and individualized medicine.
All over the world, there are millions of individuals living with HIV and the breakthrough represents a new hope to the individuals living with HIV, not only that they will get better treatment, but a cure will be found.
References and Resources
Cevaal, P. M., Kan, S., Fisher, B. M. et al. “Efficient mRNA delivery to resting T cells to reverse HIV latency.” Nature Communications 16, 4979 (2025).