Building a Better Silver Bullet: Current Status and Perspectives of Non‐Viral Vectors for mRNA Vaccines

In recent years, messenger RNA (mRNA) vaccines have exhibited great potential to replace conventional vaccines owing to their low risk of insertional mutagenesis, safety and efficacy, rapid and scalable production, and low-cost manufacturing. With the great achievements of chemical modification and sequence optimization methods of mRNA, the key to the success of mRNA vaccines is strictly dependent on safe and efficient gene vectors. Among various delivery platforms, non-viral mRNA vectors could represent perfect choices for future clinical translation regarding their safety, sufficient packaging capability, low immunogenicity, and versatility. In this review, the recent progress in the development of non-viral mRNA vectors is focused on. Various organic vectors including lipid nanoparticles (LNPs), polymers, peptides, and exosomes for efficient mRNA delivery are presented and summarized. Furthermore, the latest advances in clinical trials of mRNA vaccines are described. Finally, the current challenges and future possibilities for the clinical translation of these promising mRNA vectors are also discussed.