The 2023 Nobel Prize in Physiology or Medicine is awarded to Katarin Carrico and Drew Weisman. The winners’ work led to the development of COVID-19 vaccines, averting millions of deaths around the world.this Nobel Prize Press Release This scientific breakthrough is described in more detail:
Karikó and Weissman noticed that dendritic cells recognized in vitro-transcribed mRNA as foreign material, causing them to activate and release inflammatory signaling molecules. They wanted to know why in vitro-transcribed mRNA was considered foreign, while mRNA from mammalian cells did not elicit the same response. Karikó and Weissman realized that some key properties were necessary to distinguish different types of mRNA.
RNA contains four bases, abbreviated A, U, G and C, which correspond to A, T, G and C in DNA, the letters of the genetic code. Karikó and Weissman knew that bases in mammalian cell RNA are often chemically modified, whereas in vitro-transcribed mRNA is not. They wondered whether the absence of base changes in in vitro-transcribed RNA could explain this unwanted inflammatory response. To study this, they generated different mRNA variants, each with unique chemical changes in the bases, and delivered them to dendritic cells. The results were shocking: When the base modifications were included in the mRNA, the inflammatory response was virtually eliminated. This is a paradigm change in our understanding of how cells recognize and respond to different forms of mRNA. Karikó and Weissman immediately realized that their discovery had profound implications for using mRNA for therapeutics. These groundbreaking results were published in 2005, fifteen years before the COVID-19 pandemic.
In further studies published in 2008 and 2010, Karikó and Weissman showed that delivery of mRNA generated with base modifications significantly increased protein production compared to unmodified mRNA. This effect is due to reduced activity of enzymes that regulate protein production. By discovering that a base modification can both reduce inflammation and increase protein production, Karikó and Weissman removed a key obstacle to the clinical application of mRNA.
The New York Times reported that here.
