2. Academic Validation
  3. Interactions between mRNA lipid nanoparticles and immune cells in fresh human whole blood

Interactions between mRNA lipid nanoparticles and immune cells in fresh human whole blood

  • Eur J Pharm Biopharm. 2026 Jun 9:115146. doi: 10.1016/j.ejpb.2026.115146.
Sjoerd Hak 1,  Francesca Rodà 2,  Alicja Molska 2,  Fernando de Carlos Hernandez 2,  Camilla Wolowczyk 3,  Miriam Giambelluca 4,  Wilhelm R Glomm 2,  Sven Even Borgos 2,  Jeremie Parot 2
Affiliations

Affiliations

  • 1 Department of Biotechnology and Nanomedicine, SINTEF, Trondheim, Norway; Department of Circulation and Medical Imaging, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway. Electronic address: [email protected].
  • 2 Department of Biotechnology and Nanomedicine, SINTEF, Trondheim, Norway.
  • 3 Centre of Molecular Inflammation Research (CEMIR), Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Biomedical Laboratory Science, Faculty of Natural Sciences, Norwegian University of Science and Technology, Trondheim, Norway.
  • 4 Centre of Molecular Inflammation Research (CEMIR), Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, Norway; Department of Clinical Medicine, Faculty of Health Science, UiT- The Arctic University of Norway, Tromsø, Norway.
PMID: 42264006 DOI: 10.1016/j.ejpb.2026.115146
Abstract

Around 90 % of the drugs that enter clinical trials fail to reach the market. A main cause for this disturbing statistic is the poor correlation between drug performance in the clinic and in preclinical models of human (patho)physiology. Especially for drugs with complex structure-function relationships, such as mRNA lipid nanoparticles (mRNA-LNPs), this is problematic due to their very high dependency on large-scale preclinical screening approaches in their development. mRNA-LNPs and Other nanomedicines are often administered systemically where they interact with plasma proteins and circulating cells, which strongly affects therapeutic applications. Moreover, in various nanotherapeutic strategies, circulating immune cells may be therapeutic targets. Human whole blood is successfully used ex vivo to study human immunity, disease trajectories, and drug performance and side effects. To assess human blood's utility in mRNA-LNP development, we here screened for interactions between mRNA-LNPs and 5 immune cell types in human whole blood. We demonstrated that with only 6 blood donors and a systematically designed mRNA-LNP mini-library, it is possible to identify significant effects of different lipid ingredients on mRNA-LNP cellular uptake and cytokine induction. Our findings suggest that ex vivo use of human blood may become a valuable addition to the mRNA-LNP preclinical development pipeline.

Keywords

Human whole blood; RNA-LNP; cytokine induction; ex vivo assay; immune cell interactions; library screening; lipid nanoparticle; nanomedicine.

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