2023 Nobel Prize in Medicine: How mRNA Vaccines Revolutionized Medicine
On October 2, 2023, the Nobel Assembly at Karolinska Institutet awarded the 2023 Nobel Prize in Physiology or Medicine to Katalin Karikó and Drew Weissman for their groundbreaking discoveries in nucleoside base modifications. These discoveries unlocked the potential of effective mRNA vaccines against COVID-19, transforming the landscape of medicine.
The Journey to mRNA Vaccines
Vaccines Before the Pandemic
Vaccination has long been a crucial tool in bolstering our immune responses against pathogens. Traditionally, vaccines relied on weakened or killed viruses. For instance, the yellow fever vaccine earned Max Theiler the Nobel Prize in Physiology or Medicine in 1951. However, these methods required large-scale cell culture and posed challenges for rapid responses to outbreaks.
The Promise of mRNA Vaccines
In the 1980s, advancements in molecular biology introduced efficient methods for producing mRNA without relying on cell culture—known as in vitro transcription. This breakthrough laid the foundation for utilizing mRNA for vaccines and therapies. Yet, challenges related to stability, delivery, and inflammation dampened initial enthusiasm.
Katalin Karikó and Drew Weissman’s Collaboration
However, Katalin Karikó, a Hungarian biochemist, persevered and continued her research to harness mRNA for therapeutic purposes. In the early 1990s, she began collaboration with immunologist Drew Weissman at the University of Pennsylvania. Their collaboration focused on understanding how various RNA types interact with the immune system.
The Breakthrough Discovery
Unraveling the Immune Response
Karikó and Weissman made a crucial observation: dendritic cells treated with in vitro transcribed mRNA triggered inflammatory responses. They pondered why in vitro transcribed mRNA was perceived as foreign by dendritic cells while mRNA from mammalian cells did not elicit the same reaction. This led them to investigate the role of base modifications.
Base Modifications as the Game Changer
RNA consists of four bases: A, U, G, and C. In contrast to in vitro transcribed mRNA, mammalian cell RNA frequently features chemical modifications in these bases. Karikó and Weissman hypothesized that these alterations could mitigate the unwanted inflammatory response. Their experiments, which involved delivering various mRNA variants with unique base modifications to dendritic cells, yielded remarkable results: the inflammatory response was significantly reduced with base modifications. This discovery changeded our understanding of mRNA interactions with cells. Their findings, published in 2005—fifteen years before the COVID-19 pandemic—highlighted the immense therapeutic potential of base-modified mRNA.
Realizing the Potential of mRNA Vaccines
Enhanced Protein Production
In subsequent studies published in 2008 and 2010, Karikó and Weissman demonstrated that base-modified mRNA markedly increased protein production compared to unmodified mRNA. This was attributed to reduced activation of an enzyme governing protein production. Their discoveries eliminated critical obstacles to clinical applications of mRNA.
Speeding Up Vaccine Development
Interest in mRNA technology gained momentum, culminating in the rapid development of base-modified mRNA vaccines against SARS-CoV-2—the virus responsible for COVID-19. These vaccines boasted impressive protective effects of approximately 95% and received approval in December 2020.
Beyond COVID-19: A Promising Future
Versatile mRNA Technology
The flexibility and speed of mRNA vaccine development have opened doors to combat other infectious diseases. Moreover, this technology holds promise for delivering therapeutic proteins and treating specific cancer types.
Conclusion
Katalin Karikó and Drew Weissman’s pioneering research in mRNA modifications has ushered in a new era of medicine. Their discoveries empowered the swift development of mRNA vaccines, saving countless lives and enabling societies to regain a sense of normalcy during the COVID-19 pandemic. As we celebrate their Nobel Prize win, we recognize the transformative impact of their research on global health.
