Figure 2. mRNA contains four different bases, abbreviated A, U, G, and C. The Nobel Laureates discovered that base-modified mRNA can be used to block the activation of inflammatory reactions (secretion of signaling molecules) and increase protein production when mRNA is delivered to cells. © The Nobel Committee for Physiology or Medicine. Ill. Mattias Karlén
Topics: COVID-19, Medicine, Nobel Laureate, Nobel Prize, Physiology
has today decided to award
the 2023 Nobel Prize in Physiology or Medicine
Katalin Karikó and Drew Weissman
for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against COVID-19
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.
mRNA vaccines: A promising idea
In our cells, genetic information encoded in DNA is transferred to messenger RNA (mRNA), which is used as a template for protein production. During the 1980s, efficient methods for producing mRNA without cell culture were introduced, called in vitro transcription. This decisive step accelerated the development of molecular biology applications in several fields. Ideas of using mRNA technologies for vaccine and therapeutic purposes also took off, but roadblocks lay ahead. In vitro transcribed mRNA was considered unstable and challenging to deliver, requiring the development of sophisticated carrier lipid systems to encapsulate the mRNA. Moreover, in vitro-produced mRNA gave rise to inflammatory reactions. Enthusiasm for developing the mRNA technology for clinical purposes was, therefore, initially limited.
These obstacles did not discourage the Hungarian biochemist Katalin Karikó, who was devoted to developing methods to use mRNA for therapy. During the early 1990s, when she was an assistant professor at the University of Pennsylvania, she remained true to her vision of realizing mRNA as a therapeutic despite encountering difficulties in convincing research funders of the significance of her project. A new colleague of Karikó at her university was the immunologist Drew Weissman. He was interested in dendritic cells, which have important functions in immune surveillance and the activation of vaccine-induced immune responses. Spurred by new ideas, a fruitful collaboration between the two soon began, focusing on how different RNA types interact with the immune system.