Engineered Strategies for Enhancing mRNA Vaccine Stability in Delivery and Storage

Abstract

Messenger RNA (mRNA) vaccines have transformed immunization through their ability for quick and customizable antigen production. However, their widespread use is still limited by challenges related to the natural instability of in vitro–transcribed mRNA and the limitations of current delivery systems. Modern perspectives on stability extend beyond simple resistance to degradation. They now consider factors that can be modified through RNA structure and nanoscale environmental interactions. These interactions, which promote efficient translation, also affect the durability of these complexes against physical and chemical stresses. During formulation and storage, variables such as excipients, buffers, and solid-state architecture are essential for maintaining molecular integrity throughout manufacturing, transportation, and long-term preservation. As a result, stability serves as a key link between molecular design and overall vaccine efficacy, transforming a major obstacle into an area for strategic innovation. This review highlights recent advances at both the molecular and carrier levels aimed at developing thermostable, efficient, and highly effective mRNA vaccines, with a focus on improvements in their stability, storability, and delivery.