A Norwegian method could help researchers identify promising mRNA formulations before clinical trials. By testing lipid nanoparticles in fresh human blood, the approach captures immune reactions that conventional cell cultures may miss, but it cannot yet predict whether a medicine will be safe or effective in patients.
Researchers at SINTEF and the Norwegian University of Science and Technology have developed an experimental method for evaluating mRNA medicines in fresh human blood outside the body. Announced by SINTEF in August 2026, the work is documented in a peer-reviewed article in the European Journal of Pharmaceutics and Biopharmaceutics. It should therefore be understood as a published methodological study, not simply a research announcement.
The method addresses a central difficulty in mRNA drug development: delivering fragile genetic instructions to the intended cells without provoking unacceptable immune reactions. Messenger RNA is normally enclosed in lipid nanoparticles, or LNPs, which protect it from degradation and help it enter cells. Once inside, the mRNA instructs the cell to produce a selected protein.
LNPs are not passive packaging, however. Their composition can affect where they travel, which cells absorb them and how the immune system responds. Small changes in cholesterol, ionisable lipids or polyethylene-glycol lipids can alter particle stability, circulation time and cellular uptake.
Led by Hak, the Norwegian researchers created a systematically varied mini-library of mRNA-LNP formulations. They incubated the particles in fresh, heparinised blood from six human donors and used flow cytometry to measure their association with five immune-cell populations. Multiplex assays were used to monitor cytokines, the signalling proteins through which immune cells coordinate inflammation.
Despite pronounced differences among donors, the researchers could detect statistically significant effects associated with individual lipid ingredients. Monocytes, cells specialised in recognising and engulfing foreign material, displayed the greatest particle uptake, while T cells showed relatively little association with the formulations. Replacing cholesterol with β-sitosterol increased uptake by monocytes. Substituting PEG2000-DMG with the more persistent PEG2000-DSPE reduced cellular uptake.
These results demonstrate why human blood may provide information that simpler laboratory systems cannot. When nanoparticles enter the bloodstream, proteins attach rapidly to their surfaces and form a “protein corona”. This new biological coating can influence cellular recognition, clearance and inflammatory activity. Blood also contains complement proteins, platelets and interacting immune-cell populations that are absent from many isolated-cell experiments.
The Norwegian method belongs to an established Nordic research tradition. Scientists in Sweden and Norway have developed human whole-blood models to study how nanoparticles activate complement, coagulation, platelets, leukocytes and cytokine production. Researchers at Linnaeus University, Oslo University Hospital and other institutions have also combined blood and endothelial-cell models to investigate nanoparticle-induced vascular inflammation.
The more specific contribution from SINTEF is the application of a deliberately varied mRNA-LNP library to simultaneous screening of immune-cell uptake and inflammatory signalling. This could help developers discard poorly performing formulations before committing to expensive animal experiments or clinical trials.
The potential is supported by research elsewhere. A Pfizer study using human whole-blood assays found that mRNA-LNPs activated several immune-cell populations, induced inflammatory cytokines and stimulated the alternative complement pathway. Responses differed among blood samples from healthy donors and people with lupus, cancer or type 2 diabetes, suggesting that formulations may behave differently in medically diverse populations. The study appeared online in December 2024 and in the June 2025 issue of Molecular Therapy.
One possible application is the development of mRNA therapies intended to act on circulating immune cells. These include experimental strategies for producing chimeric antigen receptor T cells, or CAR-T cells, directly inside the body. Conventional CAR-T treatment requires cells to be extracted, genetically modified and returned to the patient. A whole-blood assay might help identify nanoparticles capable of reaching the desired immune-cell population while avoiding excessive inflammation.
Yet the method’s limitations are substantial. Six healthy donors form a small exploratory sample. Blood in a tube cannot reproduce circulation, tissue barriers, metabolism, organ accumulation, kidney or liver clearance, repeated dosing or long-term immune effects. Laboratory handling can also distort results. Norwegian research has shown, for example, that ambient air in incubation tubes can increase background complement activation.
Nor does greater cellular uptake necessarily indicate a better medicine. Uptake may occur in the wrong cells, while cytokine production may be desirable for a vaccine but dangerous in a treatment administered repeatedly. The assay measures selected biological reactions; it does not establish therapeutic efficacy or clinical safety.
No thesis specifically underlying the 2026 announcement was located. The principal scientific source is the peer-reviewed article by Hak and colleagues. Its DOI, author list, journal, volume and article number are confirmed by SINTEF’s publication repository.
The achievement should therefore be described precisely. The researchers have not replaced animal testing or demonstrated improved outcomes in patients. They have shown that fresh blood can detect formulation-dependent differences in a complex human biological environment.
If larger and independent studies establish that these signals predict clinical behaviour, the approach could become a valuable filter between laboratory development and first-in-human trials.
References
Ekdahl, K. N., Fromell, K., Mohlin, C., Teramura, Y., & Nilsson, B. (2019). A human whole-blood model to study the activation of innate immunity system triggered by nanoparticles as a demonstrator for toxicity. Science and Technology of Advanced Materials, 20(1), 688–698. https://doi.org/10.1080/14686996.2019.1625721 [tandfonline.com]
Gerogianni, A., Bal, M., Mohlin, C., Woodruff, T. M., Lambris, J. D., Mollnes, T. E., Sjöström, D. J., & Nilsson, P. H. (2023). In vitro evaluation of iron oxide nanoparticle-induced thromboinflammatory response using a combined human whole blood and endothelial cell model. Frontiers in Immunology, 14, 1101387. https://doi.org/10.3389/fimmu.2023.1101387 [frontiersin.org], [frontiersin.org]
Hak, S., Roda, F., Molska, A., de Carlos Hernandez, F., Wolowczyk, C. I., Giambelluca, M. S., Glomm, W. R., Borgos, S. E., & Parot, J. (2026). Interactions between mRNA lipid nanoparticles and immune cells in fresh human whole blood. European Journal of Pharmaceutics and Biopharmaceutics, 226, 115146. https://doi.org/10.1016/j.ejpb.2026.115146 [sintef.no]
Hestvik, I. (2026, August 27). Beyond the petri dish: Testing tomorrow’s drugs in human blood. SINTEF. https://www.sintef.no/en/latest-news/2026/beyond-the-petri-dish-testing-tomorrows-drugs-in-human-blood/ [sintef.no]
Nguyen, H.-M., Alexander, K. E., Collinge, M., Hickey, J. C., Lanz, T. A., Li, J., Sheehan, M. J., Newman, L. C., & Thorn, M. (2025). mRNA-LNPs induce immune activation and cytokine release in human whole blood assays across diverse health conditions. Molecular Therapy, 33(6), 2872–2885. https://doi.org/10.1016/j.ymthe.2024.12.019 [pmc.ncbi.nlm.nih.gov], [cell.com]
Storm, B. S., Christiansen, D., Mollnes, T. E., & Nielsen, E. W. (2020). Avoiding ambient air in test tubes during incubations of human whole-blood minimizes complement background activation. Journal of Immunological Methods, 487, 112876. https://doi.org/10.1016/j.jim.2020.112876 [pubmed.ncb…lm.nih.gov]
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