A Historical Overview on mRNA Vaccine Development

The rapid development of mRNA vaccines against COVID-19 was made possible by the cumulative knowledge and advancements across multiple scientific fields. This chapter aims to explain the key milestones on the journey toward safe and effective mRNA vaccine products and covers three main aspects: (i) the discovery, in vitro production, and optimization of mRNA as a therapeutic modality, (ii) the search for a suitable vehicle that could enable the efficient and safe delivery of intact mRNA inside cells, with an emphasis on the development of the LNP technology, and (iii) the clinical progress of mRNA vaccines starting with the first proof-of-concept studies that demonstrated the rationale of using mRNA for vaccination, followed by how mRNA vaccine design clinically evolved over more than two decades of development.