Development of Thermally Stable mRNA-LNP Delivery Systems: Current Progress and Future Prospects

The success of mRNA-LNP-based COVID-19 vaccines opens a new era for mRNA-LNP-based therapy. This breakthrough is expected to catalyze the development of more mRNA-LNP-based medicines, not only for preventive vaccines but also for therapeutic purposes. Despite the promising outlook, there are fundamental challenges impeding the progress and widespread application of mRNA-LNP formulations. One of the significant challenges is their thermal instability, requiring these products to be stored at ultralow temperatures for long-term stability. The specific requirements present significant challenges for the storage, transportation, and distribution of mRNA-LNP formulations. To effectively prepare for future infectious disease outbreaks and broaden the application of mRNA-LNP-based therapies for other illnesses, improving the thermostability of mRNA-LNP formulations is critical. In this review, we discuss the potential factors contributing to the thermal instability of mRNA-LNP formulations and examine the roles of key components such as ionizable lipids, cholesterol, pH, buffers, and stabilizing agents like sugars in maintaining their thermal stability, with the goal of providing insights that can guide the future development of thermally stable mRNA-LNP formulations.