mRNA vaccines have revolutionized biopharmaceuticals, but potency testing remains slow, costly, and highly variable. Current assays lack mechanistic insight, making it difficult to predict performance and ensure consistent quality. Industry needs faster, predictive tools to reduce development timelines and improve manufacturing reliability. These capabilities also support global health by lowering infrastructure demands and minimizing vaccine waste.
The project developed an integrated platform combining advanced potency assays with a mechanism-informed multi-scale kinetic model. This model predicts mRNA-LNP delivery and expression across nanoparticle, cellular, and population scales, linking dose, LNP size, and cell variability to potency outcomes. Experimental data from smFISH, flow cytometry, and qRT-PCR validated the model, while molecular dynamics simulations connected mRNA structural stability to translation efficiency. Embedded in a digital twin framework, the system enables real-time simulation and predictive quality control, reducing reliance on empirical testing and accelerating process optimization.
Enhance the predictive power of the potency of new mRNA vaccines and the immune response of people with different genetic backgrounds.
Improve mRNA vaccine stability and delivery process consistency.
Reduce waste during transportation and distribution.
Form a quick response to new virus variants and ensure mRNA stability and efficacy.
Accelerate the QA/QC screening for multivalent mRNA vaccine potency.
Develop and validate an efficient single-molecule RNA-fluorescence in situ hybridization (smFISH) technique-based potency assay that can track mRNA structural-functional integrity, detect RNA degradation, and monitor mRNA delivery process
Apply molecular dynamics simulations for mRNA structure-function analysis to improve the efficiency and understanding of mRNA translation
Develop a hybrid model and risk/sensitivity/predictive analysis of integrated RNA delivery and translation processes that can integrate heterogeneous measurements, identify critical root causes of the loss of potency, evaluate the value of smFISH measures, and improve the prediction accuracy of mRNA potency
The platform reduced potency testing time by more than 50% and reduce costs by up to 40%. It enables predictive QC for multivalent vaccines without additional wet-lab work and reduces cold-chain dependency, improving access in emerging markets. Validation results show strong predictive performance (R² > 0.9) and accurate dose-response and LNP size optimization.
Mechanism-Informed Multi-Scale (MIMS) Model for potency prediction
Validated assays: smFISH, flow cytometry, qRT-PCR
Digital twin integration for real-time simulation
Molecular dynamics simulations for mRNA stability
Publication: Multi-Scale Kinetics Modeling and Advanced Assay for mRNA-LNP Potency Assessment (bioRxiv, 2025)
Publication: RAPTOR-GEN: Bayesian Learning for Biomanufacturing (arXiv, 2025)
Workforce training embedded in BATL programs
Xu, W., Xie, W., (2025) RAPTOR-GEN: RApid PosTeriOR GENerator for Bayesian Learning in Biomanufacturing, ARXiv, https://doi.org/10.48550/arXiv.2509.20753
Yuchen, Y., Qui, Y., Wang, K., Liu, Y., Sanyal, G., Whitford, P., Rouhanifard, S., & Xie, W. Multi-Scale Kinetics Mideling ad Advanced Assay for mRNA-Lipid Nanoparticle Potency Assessment, BioRxIV, https://doi.org/10.1101/2025.09.29.679406
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Northeastern University
