Fig. 2

Essential breakthroughs and progress in mRNA-based treatment development. The creation of mRNA-based treatments can be split into three primary phases. Phase 1 (1961–1990) involves mRNA discovery, in vitro synthesis, and the construction of nucleic acid delivery systems, including mRNA identification, protamine uses for RNA delivery, in vitro mRNA translation, mRNA cap discovery, liposome-trapped mRNA delivery, commercialization of cap analogs and T7 RNA polymerases, cationic lipid-mediated mRNA delivery, and in vivo translation of naked mRNA through direct injection. Phase 2 (1990–2019) encompasses the accumulation of knowledge through numerous attempts and diverse applications, particularly protein replacement therapies and vaccination strategies for cancer and infectious diseases, such as mRNA-based cancer immunotherapy, founding of an mRNA-based company, 3′-UTR regulation of mRNA localization, antitumor T cell response triggered by mRNA, first clinical trial with mRNA using ex vivo transfected DCs, mRNA-based immunotherapy for human cancer, preclinical study with intranodally injected DC-targeted mRNA, protective mRNA vaccinations for influenza and respiratory syncytial virus, CRISPR-Cas9 mRNA for gene editing, and personalized mRNA cancer vaccines for clinical trials. Phase 3 (2019-present) sees mRNA-based therapeutics emerging as a disruptive technology, providing powerful and versatile tools for treating diseases, including clinical trials of mRNA vaccines for cancer and infectious diseases, as well as the emergency use of mRNA-1273 and BNT162b for the SARS-CoV-2 pandemic. Reprinted from [52] with permission from Springer Nature