mRNA vaccine platforms and novel delivery systems: From mechanistic principles to clinical translation

作者：Yunchang Yang, Yunqin Sun, Xinyao Kang, Yaofeng Wang · 发表于：Human Vaccines & Immunotherapeutics · 年份：2025 · DOI：10.1080/21645515.2025.2597629 · 被引用次数：5 · 研究领域：RNA Interference and Gene Delivery、Virus-based gene therapy research、Immunotherapy and Immune Responses

Messenger RNA (mRNA) vaccines have revolutionized the field of vaccinology, offering rapid design flexibility, scalable manufacturing, and strong immunogenicity. The unprecedented success of COVID-19 mRNA vaccines has accelerated research into novel delivery platforms and expanded therapeutic applications beyond infectious diseases to cancer immunotherapy and immune-mediated disorders. This review provides a comprehensive overview of the mechanistic principles underlying mRNA vaccine design, including mRNA engineering strategies, delivery innovations such as lipid nanoparticles (LNPs), polymeric nanoparticles (PNPs), and virus-like particles (VLPs), as well as emerging needle-free administration technologies. We further highlight recent advances in therapeutic areas spanning infectious diseases (e.g. HIV, tuberculosis, respiratory syncytial virus), oncology, and non-traditional indications such as autoimmune disorders. Despite remarkable progress, critical challenges persist in vaccine stability, delivery efficiency, large-scale manufacturing, and global accessibility. Finally, we discuss future research directions integrating artificial intelligence, nanotechnology, and systems immunology to accelerate next-generation mRNA vaccine development and clinical translation.