Mathematical modeling in mRNA therapeutics: towards a pathway to individualized treatment protocols

mRNA-lipid nanoparticle (mRNA-LNP) therapeutics represent a transformative pharmacological paradigm in which the delivery vehicle, genetic payload, and expressed protein form a tightly coupled system. This multicomponent structure introduces nonlinear, multiscale dynamics that challenge traditional pharmacokinetic and pharmacodynamic frameworks, making quantitative modeling essential.

This review provides a structured biological framework for mRNA-LNP therapeutics, detailing the key processes governing delivery, endosomal escape, mRNA stability, and translation, and highlighting their associated temporal and spatial scales, providing the key aspects to consider for modeling. Building on this foundation, we summarize mathematical modeling approaches, including pharmacokinetic (PK), pharmacodynamic (PD), physiologically based pharmacokinetic (PBPK), and quantitative systems pharmacology (QSP) models, used to represent these mechanisms. The literature was surveyed to identify representative preclinical and translational studies, focusing on model structure, assumptions, and their use in human projection and dose optimization.

Mathematical models are increasingly critical to interpret and predict mRNA therapeutic behavior, yet challenges remain in parameter identifiability, data availability, and model standardization. Future advances will depend on biologically grounded modeling frameworks, improved integration of mechanistic insight with quantitative approaches, and tighter coupling between experimental design and model development. These developments will support more efficient translation and enable precision medicine applications.

Abstract from PubMed (PMID 42969431). This entry was added automatically by our daily literature monitor because it matches the topics we follow; read the full paper at the original source.