Authors
Elio Campanile, Elisa Pettinà, Stefano Giampiccolo, Lorena Leonardelli, Luca Marchetti
Published in
Molecular therapy. Nucleic acids. Volume 37. Issue 3. Pages 103002. Sep 08, 2026. Epub Jul 08, 2026.
Abstract
Antibody-based therapeutics has revolutionized disease treatment, and recent advances in messenger RNA (mRNA) technologies have opened new opportunities for their intracellular production. In particular, in vitro-transcribed mRNA encapsulated in lipid nanoparticles (LNPs) enables targeted delivery to specific cells, where it can enable the synthesis of therapeutic antibodies with prolonged half-lives in a cost-effective manner. Despite rapidly growing experimental data, a modeling framework that integrates mRNA delivery, intracellular expression kinetics, and whole-body antibody disposition remains unavailable. To address this gap, we extended a physiologically based pharmacokinetic model with a novel multiscale layer describing mRNA trafficking, cellular uptake, translation, and degradation. The integrated model was calibrated and validated using five datasets of mRNA-based cancer therapeutics, demonstrating strong predictive performance for the biodistribution of mRNA-encoded antibodies. The newly introduced mRNA layer, while minimally parameterized, effectively represents complex intracellular and systemic processes, enabling quantitative investigation of antibody biodistribution, optimization of dose scheduling, and providing an initial framework for future exploration of how LNP-mRNA formulation influences delivery and pharmacokinetics.
PMID:
42568897
Bibliographic data and abstract were imported from PubMed on 08 Aug 2026.
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