Early Spectroscopic Insights into RNA Modifications in LNP Formulations with Microfluidic Modulation Spectroscopy

Abstract

This application note explores the use of Microfluidic Modulation Spectroscopy (MMS) to detect early structural changes in RNA exposed to lipid nanoparticle (LNP) formulation conditions. Using polyA and polyC RNA models, the study simulates SM-102-driven degradation pathways, including aldehyde adduct formation and acid-catalyzed base loss. MMS revealed distinct IR spectral shifts—like new absorbance bands and loss of aromatic signatures—suggesting either ring nitrogen adduct formation or abasic site generation. These results show MMS’s ability to differentiate degradation mechanisms in RNA with minimal sample prep, offering a fast, label-free method for preclinical quality assessments in mRNA therapeutics.