Design strategies to optimize polymeric vectors for mRNA delivery

mRNA holds great promise for preventing and treating a variety of diseases, from infectious diseases to diverse cancers, owing to its transient expression, lack of genomic integration, and scalable production. Among non-viral vectors, polymeric carriers are attractive due to their synthetic versatility and stability, which allow for precise tuning for efficient mRNA delivery. Their scalability further supports the applicability of polymeric vectors. Studies have addressed the room for improvement in polymeric systems for mRNA delivery and have adapted varying approaches depending on the type of polymeric structure, including but not limited to PEGylation, hydrophobic modification, and incorporation of responsive or targeting moieties. This review summarizes advances in polymeric vectors for mRNA delivery and highlights how distinct structural modifications influence toxicity, mRNA transfection efficiency, biodistribution, intracellular trafficking and immune activation, providing a framework for the rational design of next-generation polymeric vectors that can fully realize the clinical potential of mRNA therapeutics.