The 2023 Nobel Prize in Medicine has been awarded jointly to Katalin Karikó and Drew Weissman for research that was critical in the development of mRNA vaccines against Covid-19.
The Nobel committee honored Hungarian-born biochemist Karikó and US immunologist Weissman “for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against Covid-19.”
Karikó and Weissman started working together at the University of Pennsylvania in the US in the 1990s. While Karikó had been devoted to developing methods to use mRNA for therapy, Weissman was interested in dendritic cells, which have important functions in immune surveillance and the activation of a vaccine-induced immune response.
Together, they began to focus on how different types of RNA interact with the immune system.
Work that led to the Medicine Nobel Prize
During their collaboration, they noticed that an immune response was triggered when they introduced dendritic cells to mRNA produced without cell culture. This is also known as in vitro transcribed mRNA.
They were intrigued as to why in vitro transcribed mRNA triggered this reaction while mRNA from mammalian cells did not. The two realized that there must be key differences in the properties of the two types.
They knew that the nucleotide bases in RNA from mammalian cells were frequently modified, while the bases in in vitro transcribed mRNA were not and wondered if this could provide an explanation.
To test their theory, they produced different variants of mRNA, each with unique modifications in their nucleotide base sequences, which they then delivered to dendritic cells. They found that in all cases where the mRNA bases had been modified, the immune response was suppressed.
This discovery fundamentally changed understanding of how mRNA interacts with the human immune system. Their findings were published in 2005, fifteen years before the onset of the Covid-19 pandemic.
In later studies, they showed that in addition to reducing the inflammatory response, mRNA with base modifications also increased protein production due to reduced activation of an enzyme that regulates protein production.
In 2020, at the start of the Covid-19 pandemic, Pfizer–BioNTech and Moderna chose to use mRNA with modified bases to develop their vaccines against the virus, building on the discoveries made by Karikó and Weissmann.
Several other vaccines against Sars-CoV-2, based on different methodologies, were also rapidly introduced, and together, more than thirteen billion Covid-19 vaccine doses have been administered globally. In addition to Covid-19, mRNA vaccines are being developed for an array of other diseases.
“Katalin Karikó and Drew Weissman are brilliant researchers who represent the epitome of scientific inspiration and determination,” said Penn President Liz Magill. “Day after day, Dr. Weissman, Dr. Karikó and their teams worked tirelessly to unlock the power of mRNA as a therapeutic platform, not knowing the way in which their work could serve to meet a big challenge the world would one day face.”
“With the truest devotion to their field, they’ve already promised they will not stop here, and that is the greatest inspiration of all,” Magill added. “Our Penn community is enormously proud of their groundbreaking achievements and this well-deserved recognition.”