ArticleMolecular therapy. Nucleic acids2026
Multiscale modeling guided potency assessment of mRNA-lipid nanoparticles.
Article in Molecular therapy. Nucleic acids, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
mRNA lipid nanoparticle (mRNA-LNP) technology has emerged as a cornerstone in vaccine development due to its high delivery efficiency, molecular stability, and favorable safety profile. However, rapid and reliable potency assessment remains challenging because of limited mechanistic understanding of delivery processes and sparse experimental data. To address these gaps, we introduce a mechanism-informed, multi-scale kinetic modularized modeling framework that quantitatively captures the coupled dynamics of mRNA delivery across nanoparticle, cellular, and macroscopic scales. The model incorporates variability in LNP-cell interactions and integrates key determinants, such as dosage, LNP and cell size distributions, cell proliferation, and membrane properties-factors that critically shape delivery efficiency and response heterogeneity. Its cell-based architecture and modular design enable adaptability to diverse delivery systems and physiological contexts. By leveraging advanced multi-omics assays, including single-molecule fluorescent
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