Expert review of vaccinesDec 3, 2025

Making mRNA vaccines more stable at higher temperatures

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

Improving mRNA-LNP vaccine thermostability likely requires coordinated changes across RNA design, formulation, excipients, and manufacturing.

Evidence

This review covers mechanisms of mRNA-LNP instability and stabilization strategies including sequence optimization, nucleotide modification, LNP design, process optimization, lyophilization, dual-vial formats, and deep eutectic solvents.

Caveat

The abstract synthesizes development strategies rather than reporting a single validated formulation that reliably supports refrigerated or room-temperature storage.

Simplified

INTRODUCTION: One of the biggest challenges in the mRNA-LNP vaccine field is product stabilization to overcome the logistical hurdles linked to the ultra-cold distribution chain associated with first-generation mRNA SARS-CoV-2 vaccines. Despite recent progress in the field, many R&D efforts remain focused on the development of mRNA-LNP vaccines that would be as stable as liquid formulations for storage at refrigerated or room temperatures.

AREAS COVERED: After an overview of the underlying mechanisms of mRNA-LNP instability, this review provides an update on the different approaches that are currently explored to improve mRNA-LNP thermostability, encompassing mRNA sequence optimization, nucleotide modification and mRNA-LNP design strategies as well as formulation process optimization. Alternative approaches for mRNA-LNP stabilization such as lyophilization, dual-vial formulations and the replacement of water with deep eutectic solvents in the mRNA-LNP process and products are also discussed.

EXPERT OPINION: Achieving robust thermostability of mRNA vaccines will require a multifactorial optimization strategy, integrating advances in sequence engineering, novel formulation designs, buffer composition, excipient selection and manufacturing processes.