Researchers test a new type of medicine – outside the body

The Covid-19 vaccine is perhaps the first thing many people think of when they hear about drugs based on mRNA.

Small packages of genetic material are sent into the body, where they make our cells produce useful proteins in the fight against the virus.

But the list of diseases that can potentially be treated with mRNA-based medicines is far more extensive than just those preventable with vaccines.

mRNA is expected to be used in treating conditions such as cardiovascular diseases, rare hereditary diseases, and autoimmune diseases. And, not least, cancer.

“Almost all diseases we know are caused by some protein or another. Either there’s too much protein, or too little, or the protein has a defect. Proteins are encoded by mRNA. The potential for mRNA drugs is therefore enormous. They will be a very important tool,” says researcher Sjoerd Hak.

He works at SINTEF’s Department of Biotechnology and Nanomedicine. The researchers have now tried out a new method that will make it easier to develop new forms of this type of medicine.

“90 per cent of all drugs that are tested in clinical trials on humans are not approved. Therefore, it is important to be able to identify the best drugs and weed out the bad candidates before you get to that point,” says Hak.

Trial and error

A major reason why so many drugs fail during testing is the big difference between humans and the animals used in preclinical testing. These are tests carried out before trials in humans.

What may look promising when tested in mice may have zero effect or even cause serious side effects when injected into the bloodstream of a patient.

mRNA is unstable and has to be packaged inside small fat particles. These are called lipid nanoparticles (LNPs). These fat particles transport mRNA into cells.

When the tiny particles are injected into the blood, the outer fatty layer will bind to proteins in the blood plasma, and the nanoparticle will encounter immune cells circulating in the blood. What happens next – whether the immune cell 'eats' the particle and what happens inside the immune cell afterwards – will determine the effect of the medicine.

“LNPs can be made in a thousand different ways. How they are put together is crucial for how the mRNA will enter the cells and function as medicine. That's why you have to create and test a lot of different variants,” says Hak.

Human blood as a test environment

Hak and his colleagues have now looked at how to test the drugs in human blood from donors instead of injecting the medicines into the body.

Using fresh blood that contains all of the blood cells and plasma, the researchers tested different mRNA-LNP particles and examined how they were taken up by immune cells in the blood.

They also looked at which signal substances the cells produced. Signal substances control the immune response and are an important part of how the drugs work.

The results show that this method enables researchers to see which variants of mRNA-LNP had the greatest uptake in the immune cells, and which ones triggered strong or weak activation of the immune system.

“The results show that testing with this kind of blood outside the body could be a useful addition to today’s preclinical testing in laboratory animals,” says Hak.

Since the researchers use human blood, the results can reveal more about what actually happens in humans than animal experiments can.

“At the same time, it's important to state that this testing is only a small piece of the bigger puzzle. But it allows you to decide earlier on whether it's worth continuing. You can weed out bad trial candidates at an early stage and instead select the ones that are most promising. And you can do it not only in mice, but also in human blood,” says Hak.

The method could make cancer treatment cheaper

Hak highlights the new CAR-T therapy as an example of a treatment where testing in human blood could offer advantages. CAR-T is a type of immunotherapy that has shown remarkable results in treating certain types of cancer.

Currently, the T cells are removed from the patient and modified in a lab so that they can recognise cancer cells. The cells are then injected back into the patient. Researchers are now working on carrying out this process directly inside the body.

With mRNA technology, it is in principle possible to modify these cells inside the patients.

"In principle, you can inject mRNA into the blood, which will then find the immune cells and give them the right receptor. If successful, this method could reduce costs dramatically and make the treatment available to more people," says Hak.

He believes this is a good example of a therapy that could first be tested in human blood.

The researcher explains that immune cells circulate in the blood. Researchers can therefore test the treatment in human blood and quickly see whether it appears to work.

They can cause allergic reactions

Hak also believes that testing in human blood could reduce the risk of serious side effects when new medicines are tested in humans.

“An important aspect of nanomedicines and mRNA-LNPs is that they can cause allergic reactions. There are some drugs where as many as half of the people who receive them have an allergic reaction,” he says.

Many patients do not experience serious reactions. But for a few, the reaction can be fatal.

“As of today, we don’t have good enough models to detect such effects. They’re difficult to predict. But blood has been shown to be a good predictor of such allergic reactions. By testing the medicine in blood samples first, we can better predict allergic reactions. This way, we hope to avoid people becoming seriously ill when the medicines are tested,” says Hak.

Reference:

Hak et al. Interactions between mRNA lipid nanoparticles and immune cells in fresh human whole blood, European Journal of Pharmaceutics and Biopharmaceutics, 2026. DOI: 10.1016/j.ejpb.2026.115146

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Read the Norwegian version of this article on forskning.no

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