Rapid Electrophoretic Assay of mRNA Vaccine Quality Attributes

This project goal is to develop a method to rapidly assess critical quality attributes (CQA) of mRNA lipid nanoparticles (LNPs) used in mRNA vaccines.

Industry Need

HPLC, used for mRNA quality control, requires significant solvent and maintenance expenses.
Throughput of HPLC is limited because it requires extensive wash and conditioning steps.
Additionally, gel electrophoresis methods, widely used in lab-scale testing of mRNA for LNPs, are too slow to be useful in this size range, have long run times, and require frequent replacement to maintain peak sharpness.

Solution

Carnegie Mellon aims to develop a means to rapidly assess CQAs of mRNA LNPs used in mRNA-based vaccines through capillary electrophoresis (CE). The method is a form of capillary electrophoresis (CE), a widely accepted, miniaturizable, and easily deployed analytical technique, with several commercial platforms available for use in biomanufacturing facilities and clinical diagnostic labs. CE uses a rapid, surfactant-based form of electrophoretic DNA and RNA separation that characterizes size resolution appropriate for mRNA used as vaccine feedstocks.

Carnegie Mellon University will present:

A rapid means to characterize mRNA quality prior to LNP encapsulation
A rapid means to characterize mRNA quality following release from LNPs
A combination method that quickly measures LNP surface charge and mRNA payload quality – two CQAs linked to vaccine effectiveness. This method could be used to assay mRNA quality following their synthesis by in vitro transcription, to study the impact of shelf life and temperature history on the physical properties of mRNA LNPs, and even to verify the quality of mRNA vaccines at point-of-use.

Outcomes and Impacts

The project will demonstrate a transformative means to rapidly and accurately characterize nanoparticles used in COVID-19 vaccines.

Since electrophoresis instrumentation is relatively cheap and easy to use, the method established could be deployed in biomanufacturing and routine testing of stocks at point-of-use to ensure product safety.

Updates, Related Publications, and Deliverables

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Project Lead

Carnegie Mellon University