2023 Nobel Prize in Medicine Awarded for Development of mRNA Vaccines Against COVID-19

On Oct. 2, 2023, The Nobel Prize in Physiology or Medicine was awarded jointly to Katalin Karikó and Drew Weissman for their work on nucleoside base modifications that allowed the development of effective messenger RNA (mRNA) vaccines against COVID-19. The duo’s groundbreaking discoveries were crucial in the current international understanding of how mRNA interacts with the immune system; their work played a crucial role in the rapid rate of vaccine development during the global pandemic.

Karikó and Weissman began their collaboration during the 1990s at the University of Pennsylvania. Karikó, then an assistant professor, was committed to developing mRNA as a therapeutic, despite difficulties in receiving funding. Enthusiasm for mRNA research was limited at the time; though the introduction of in vitro transcription in the 1980s spurred molecular biology development, in vitro transcribed mRNA was unstable, requiring lipid systems to encapsulate the mRNA. The treatment also heightened inflammatory reactions. But Weissman, a new colleague of Karikó, proved to be the perfect partner for her research. As an immunologist, he worked primarily with dendritic cells, which are vital to immune surveillance and activating vaccine-induced immune responses. Together they began to focus on the interaction of different RNA types with the immune system.

Karikó and Weissman’s breakthrough came when they began studying why dendritic cells recognized in vitro transcribed mRNA as a foreign substance, while mRNA from mammalian cells did not have the same response. They knew that the bases of RNA from mammalian cells are often chemically modified, while in in vitro transcribed mRNA is not. Karikó and Weissman produced variants of mRNA with different chemically altered bases and found that when those mRNA were delivered to dendritic cells, the inflammatory reactions were almost completely abolished. This discovery fundamentally altered the understanding of how cells recognized and respond to mRNA.

In 2005, Karikó and Weissman published the results of their research, 15 years before the COVID-19 pandemic began. In later studies published in 2008 and 2010, they proved that mRNA with base modifications shows a significant improvement in protein production compared to unmodified mRNA. Thanks to their findings, the two major roadblocks in mRNA development had been eliminated, and several companies began working to develop the method. And after the COVID-19 outbreak, two base-modified mRNA vaccines were able to be developed at record speed. The Nobel prize honors the work of Karikó and Weissman, and the critical role it played in combatting one of the greatest health crises of the modern age.

Source: Nobel Prize