Peptides: potential delivery systems for mRNA.

mRNA-based therapies have broad applications in various disease treatments and have been applied in protein replacement therapy, gene editing, and vaccine development. Numerous research studies have been carried out aiming to increase the stability of mRNA, improve its translational efficiency, and reduce its immunogenicity. However, given mRNA's large molecular size and strong electronegativity, the safety and efficient delivery of mRNA into the target cells remains the critical rate-limiting step in current mRNA drug development. Various nanocarriers, such as liposomes, lipid nanoparticles, polyetherimide, and mesoporous silica nanoparticles, have been employed for mRNA delivery in the past few decades. Among them, peptides have demonstrated great potential as promising carrier candidates for mRNA delivery due to their high cell membrane permeability, good biocompatibility, definite chemical structure, and ease of preparation. Here, peptide-based mRNA delivery systems are systematically analyzed, including their construction strategies, mechanisms of action in mRNA delivery, and the application limitations or challenges. It is hoped that this review will guide the design, optimization, and applications of peptide carriers in mRNA-based drug development.