ElectrophoresisJan 30, 2026

Methods to concentrate mRNA and mRNA nanoparticle formulations for measuring mRNA quality at low levels

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Feb 1, 2026

Abstract

Two concentration methods were established to enhance the stability and integrity of RNA formulations, including mRNA-lipid nanoparticles.

Freeze-drying and ultrafiltration methods were developed for concentrating low-abundance RNA solutions.
These methods are applicable to mRNA, mRNA-lipid nanoparticles, and self-amplifying RNA formulations.
Concentrated RNA products demonstrated superior storage stability compared to their dilute counterparts.
High-performance liquid chromatography analyses confirmed the structural and molecular integrity of the concentrated RNA.

Simplified

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.

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Methods to concentrate mRNA and mRNA nanoparticle formulations for measuring mRNA quality at low levels

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