The Nobel Assembly at Karolinska Institutet has awarded the 2023 Nobel Prize in Physiology or Medicine jointly to Katalin Karikó and Drew Weissman for their discoveries that enabled the development of mRNA vaccines against Covid-19.
In a statement, the Assembly said: “The discoveries by the two Nobel Laureates were critical for developing effective mRNA vaccines against Covid-19 during the pandemic that began in early 2020. Through their groundbreaking findings, which have fundamentally changed our understanding of how mRNA interacts with our immune system, the laureates contributed to the unprecedented rate of vaccine development during one of the greatest threats to human health in modern times.”
Katalin Karikó, a Hungarian biochemist, worked with immunologist Drew Weissman in the early 1990s when she was an assistant professor at the University of Pennsylvania.
Karikó and Weissman noticed that dendritic cells recognise in vitro transcribed mRNA as a foreign substance, which leads to their activation and the release of inflammatory signalling molecules. They realised that some critical properties must distinguish the different types of mRNA.
They produced different variants of mRNA, each with unique chemical alterations in their bases, which they delivered to dendritic cells, and found that the inflammatory response was almost abolished when base modifications were included in the mRNA. The discovery had profound significance for using mRNA as therapy.
In further studies published in 2008 and 2010, Karikó and Weissman showed that the delivery of mRNA generated with base modifications markedly increased protein production compared to unmodified mRNA. The effect was due to the reduced activation of an enzyme that regulates protein production.
Through their discoveries that base modifications both reduced inflammatory responses and increased protein production, Karikó and Weissman had eliminated critical obstacles on the way to clinical applications of mRNA.
Read DDW’s In-Focus eReport to find out more about uses for mRNA technology and its future applications.
Image credit: Ill. Niklas Elmehed © Nobel Prize Outreach
