Roadmap to the Development of mRNA Therapeutics: From Molecule Design and Delivery Strategies to Manufacturing, Quality Control, and Regulatory Considerations

mRNA has been touted as a therapeutic modality since 1990 and has demonstrated potential applications in oncology, protein replacement therapies, and infectious diseases. Since the first demonstration of direct injection of mRNA into muscle showing expression of the encoded protein, tremendous progress has been made to improve mRNA functionality, stability, and safety. Progress has also been made with the development of specialized drug delivery systems that enable delivery of mRNA to virtually any organ, tissue, and cells in the body. The rapid development and deployment of mRNA vaccines to address the COVID-19 global pandemic is a true testimony of the significant developments of mRNA technology in the past 30 years. In this book chapter, we will review design strategies used to improve mRNA functionality, stability, and safety and delivery strategies that have been used to deploy mRNA vaccines and provide an overview of manufacturing technologies and regulatory challenges. We will present our own perspective in these areas, gained through building an end-to-end mRNA discovery and development platform to evaluate therapeutic mRNA as a rapid response to pandemic threats and pandemic prevention.