mRNA Stability and Structural Hierarchy
Project Description
mRNA vaccines are a promising approach to preventing infectious disease and treating some forms of cancer, but they are remarkably unstable, and current understanding of the factors controlling mRNA degradation is poor. This limits our ability to rationally design chemically modified mRNA and stable vaccine formulations, strains distribution networks, and compromises global access. This Gilbreth Fellow will work toward developing a hierarchical understanding of mRNA degradation rates and mechanisms across length scales: from nucleotide sequence, to folded structure, to intermolecular complexes, to lipid nanoparticles (LNPs), to bulk formulation. Research in each area will combine experiment and modeling to address mRNA/RNA stability, with the goal of accurately predicting the rate and sites of degradation and suggesting stabilizing interventions (e.g., chemical modification, formulation).
The ability to accurately predict mRNA degradation rates from primary sequence and formulation variables would greatly reduce the field’s dependence on time-consuming stability studies, shorten development timelines, and enable rapid deployment of mRNA vaccines to promote public health.
Start Date
Spring, Summer or Fall 2026
Postdoc Qualifications
Expertise in lipid nanoparticle fabrication, computational modeling, RNA analysis, or formulation stability are encouraged. The Fellow will have opportunities to collaborate with a multi-disciplinary team across these and other fields between Purdue and NIBRT in Ireland.
Co-advisors
Elizabeth Topp, ChE/IMPH, https://engineering.purdue.edu/ChE/people/ptProfile?resource_id=240700
Kurt Ristroph, ABE, https://www.ristrophlab.com/
Bibliography
Comparative Analysis of mRNA Degradation Kinetics Using Chromatographic and Electrophoretic Methods, https://doi.org/10.1021/acs.molpharmaceut.4c01543
Mechanistic insights into how mixing factors govern polyelectrolyte-surfactant complexation in RNA lipid nanoparticle formulation, https://doi.org/10.1016/j.jcis.2024.08.150
Phosphodiester models for cleavage of nucleic acids, https://doi.org/10.3762/bjoc.14.68