Developing mRNA for therapy: My journey

Messenger RNA was discovered in 1961 and it took 60 years until the first mRNA became FDA-approved product in the form of COVID-19 mRNA vaccine. During those years a lot of progress has been made by hundreds of scientists. First, isolated mRNAs were structurally and functionally characterized. In 1978 isolated mRNA delivered into mammalian cells were shown to produce the encoded protein. In vitro transcription - introduced in 1984 - made it possible to generate mRNA coding for any desired protein from the corresponding DNA by using phage RNA polymerases. In the early 90s in vitro-transcribed mRNA was mainly tested in animals as vaccine against infectious diseases and cancer. A great extent of progress toward a viable treatment was made during those years but the inflammatory nature of mRNA initially hampered its medical use. Together with my colleagues, we achieved a great milestone when we warded off the response by replacing uridine with pseudouridine in mRNA. We further demonstrated that nucleoside-modified mRNA formulated with lipid nanoparticles can be a potent vaccine. These discoveries eventually led to the development of the mRNA vaccine that has helped to fight the global COVID pandemic and opened the door for developing breakthrough therapeutics for incurable diseases and unmet medical needs.