LNP-mRNA Vaccine Stability: Reference Materials, Rapid Stability Assessment and Lyophilized Formulation Development

The goal of this project is to develop and characterize LNP-mRNA drug product reference materials and to produce stable mRNA vaccines at higher temperature.

Industry Need

This project seeks to help improve LNP-mRNA vaccine stability by developing and characterizing LNP-mRNA drug product reference materials that will mimic current COVID-19 vaccine characteristics, deploying LNP-mRNA reconstituted drug product physiochemical and functional critical quality attribute assays for characterization, formulation and stability assessment of reference materials.

Solution

Rensselaer and Carnegie Mellon will take the following steps during this project:

The mRNAs will be formulated as LNPs with lipid compositions and mRNA loadings mimicking the known compositions of current COVID-19 vaccines.
Reference materials will serve as a testbed for the routine evaluation of mRNA length and structure on the stability of LNP-mRNA drug project product and stability of lyo LNP-mRNA formulation compositions.
Physicochemical testing will include assays to characterize mRNA integrity, primary structure, and secondary structure and LNP size, surface charge and RNA payload integrity.
The LNP-mRNA reference materials, representing a range of mRNA lengths and structure distributions, will be further formulated using cryoprotectants and lyoprotectants, and lyophilized over a range of freezing, primary drying and secondary drying time-temperature profiles.

Additionally, the team will develop room temperature stable lyo LNP-mRNA drug product formulations and lyo processes which take into account the characteristics of the mRNA payload.

Outcomes and Impacts

By demonstrating freeze-drying approaches for mRNA-based vaccines as a function of mRNA length and structure that will produce stable material at higher temperatures, this project can further impact domestic and global vaccine distribution by simplifying the cold-chain and reducing lost/wasted doses.

Updates, Related Publications, and Deliverables

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Project Lead

Rensselaer Polytechnic Institute

Participating Organizations

Carnegie Mellon University