Next-Generation Polymeric mRNA Nanocarriers: From Chemical Engineering to Organ-Selective Gene Delivery

mRNA-based therapeutics as an emerging biotherapeutic platform offers immense potential in various fields, including vaccine development, tumor immunology, protein replacement therapy, and gene editing. However, critical bottlenecks persist, including poor stability, inherent immunogenicity, and low targeted delivery efficiency. Polymer carriers, characterized by their programmable structure, adaptable functionalization, and good biocompatibility, have emerged as a pivotal strategy to overcome these translational challenges for mRNA therapeutics. Compared with lipid nanoparticles (LNPs), polymeric carriers offer distinct advantages in mitigating mRNA instability, inherent immunogenicity, and achieving extrahepatic delivery. This review initially outlines the biomedical applications of mRNA therapy. We focus on the latest advancements in polymeric carriers for mRNA delivery, emphasizing the significance of chemical structure diversity and rational design. Furthermore, we summarize breakthroughs in non-liver-targeted delivery strategies utilizing these carriers. Finally, the review identifies current challenges for polymeric carriers. Looking forward, it is imperative to integrate advanced synthetic techniques and rationally engineer structural designs, ultimately enabling the comprehensive application of mRNA therapy in precision medicine. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.