POSTER

Advancing mRNA Manufacturing and Characterization:
Comprehensive Analytical Capabilities for mRNA
Therapeutics

Pol Harvengt , Maha Dridi, Wei Rong, Bruna Martins, Michael Lambin, Jérôme Laval, Mélanie Duyck, Hanna P. Lesch

Abstract

    The growing demand for high-quality mRNA therapeutics necessitates robust manufacturing and analytical solutions to ensure product integrity, efficacy, and regulatory compliance. Our in-house Ntensify™ mRNA manufacturing technology provides a scalable and GMP-compliant platform for mRNA production. Beyond manufacturing, we have developed a comprehensive portfolio of advanced analytical tools for mRNA characterization, supporting a broad range of critical quality attributes required for mRNA release testing. Using nanopore sequencing, we achieve full-length mRNA sequence verification and poly(A) tail characterization with high resolution. Liquid chromatography-mass spectrometry (LC-MS) enables precise analysis of capping efficiency, while also providing impurity profiling. Off-the-shelf automated solutions for nucleic acids profiling must also be adapted to accommodate the novel requirements of mRNA vaccines. This is the case of automated capillary electrophoresis systems that we divert in house to accommodate the profiling of long self-amplifying RNAs or to evaluate plasmid linearization efficiency.  A sensitive assay for double-stranded RNA (dsRNA) quantification was developed in house to control the load of this immunogenic contaminant. Minimizing unwanted innate immune responses is a key challenge in mRNA therapeutics and is alternatively addressed in our group with a reporter cell-based assay. Additional cell-based expression assays for formulated products allow functional in vitro testing to confirm mRNA translation efficiency and biological activity post-formulation. Far from being straightforward, these assays must often be tailored to the lipid composition of the LNP. To facilitate accurate characterization, we have also developed optimized lipid nanoparticle (LNP) disruption methods that efficiently release encapsulated mRNA, making it more accessible for analysis. Our integrated manufacturing and analytical capabilities ensure a streamlined workflow from mRNA production to final release, meeting the stringent quality requirements for clinical and commercial applications.

    Poster WVC 2025