Concentration Approaches for mRNA and mRNA–LNP Formulations: Enabling mRNA Integrity Quantification in Low‐Concentration Formulations

ABSTRACT mRNA‐based vaccines and self‐amplifying mRNA (saRNA) have gained growing attention for disease prevention and treatment, but precise detection of low‐concentration RNA (including mRNA–lipid nanoparticles, mRNA–LNPs) stability and integrity remains challenging—limiting quality control of RNA‐based therapeutics. Capillary electrophoresis (CE)‐based instruments show potential, yet suitable concentration strategies for low‐abundance, labile RNAs are lacking. This study established two distinct concentration methods (freeze‐drying and ultrafiltration) applicable to mRNA, mRNA–LNPs, and saRNA formulations, enabling the conversion of dilute solutions to high‐concentration preparations while preserving the structural and molecular integrity of the target nucleic acids. Subsequent stability evaluations and conventional high‐performance liquid chromatography analyses of the concentrated products verified their superior storage stability and strong practical applicability. This article aims to reduce the difficulty of RNA integrity assessment and improve the accuracy of detecting various low‐concentration RNA samples that may arise in the future.