Benchmarking emerging chromatographic platforms for mRNA-LNP characterization and scalable process enablement

Vollständiger Abstract

Worum geht es in dieser Arbeit?

Lipid nanoparticles (LNPs) are now the leading delivery platform for nucleic acid therapeutics, supporting applications from prophylactic mRNA vaccines to in vivo gene editing, in vivo CAR-T, protein replacement, and personalized cancer immunotherapy. As formulations incorporate novel ionizable lipids, targeting ligands, and multi-component payloads, analytical complexity increases, and no single method can capture all critical quality attributes (CQAs). This study benchmarks the PATfix LNP Switcher Platform against established (RiboGreen, DLS) and emerging (FFF-UV-MALS-DLS-RI) techniques. The 2D LNP Switcher uses independent flow paths, dual UV-Vis/MALS detection, and automated switching between non-disruptive and denaturing modes, enabling preparation-free analysis of intact particles followed by online disruption to quantify encapsulated nucleic acid, free mRNA, and lipid–mRNA adducts. This platform supports integrated, multi-parameter LNP characterization that aligns process development, manufacturing, and evolving regulatory expectations, and complements the scalable, preparative purification of mRNA-LNPs on CIMmultus OH monoliths.