Advanced nanoscale delivery systems for mRNA-based vaccines

The effectiveness of messenger RNA (mRNA) vaccines, especially those designed for COVID-19, relies heavily on sophisticated delivery systems that ensure efficient delivery of mRNA to target cells. A variety of nanoscale vaccine delivery systems (VDSs) have been explored for this purpose, including lipid nanoparticles (NPs), liposomes, and polymeric nanoparticles made from biocompatible polymers such as poly(lactic-co-glycolic acid), as well as viral vectors and lipid-polymer hybrid complexes. Among these, lipid nanoparticles (LNPs) are particularly notable for their proficiency in encapsulating and protecting mRNA. These VDSs can be engineered to enhance stability and facilitate uptake by cells. The choice of delivery system depends on factors like the specific mRNA vaccine, target cell types, stability requirements, and desired immune response. In this review, we shed light on recent advances in delivery mechanisms for self-amplifying RNA (saRNA) vaccines, emphasizing groundbreaking studies on nanoscale delivery systems aimed at improving the efficacy and safety of mRNA/saRNA vaccines.