On October 2, 2023, the Nobel Committee announced that this year’s Nobel Prize in Physiology or Medicine would be jointly awarded to Katalin Karikó and Drew Weissman for their discoveries in nucleoside modification, which have greatly accelerated vaccine development, including vaccines against COVID-19.

Katalin Karikó, born in Hungary, currently serves as the Vice President of BioNTech, a German pharmaceutical company. Drew Weissman, born in Lexington, Massachusetts, USA, is the Roberts Family Professor of Vaccine Research and the Director of the Penn RNA Innovation Institute at the University of Pennsylvania. The research and discoveries of Karikó and Weissman laid the foundation for the rapid development of messenger RNA (mRNA) vaccines, helping humanity navigate through the COVID-19 pandemic.

In the early 21st century, while collaborating at the University of Pennsylvania, Karikó and Weissman noticed that dendritic cells of the immune system recognize externally transcribed mRNA as foreign, leading to their activation and the release of inflammatory signaling molecules. They realized that the genetic information carried by mRNA is not limited to the four bases A, U, C, and G but also includes various mRNA chemical modifications. RNA in mammalian cells is often chemically modified, unlike externally transcribed mRNA. Could these base modifications be the key?

To test this idea, they produced different variants of mRNA, each with unique base modifications, and delivered them to dendritic cells. The results were astonishing: when mRNA contained base modifications, the inflammatory response was nearly eliminated. This groundbreaking research was published in 2005. By discovering that base modifications could both reduce inflammation and increase protein production, Karikó and Weissman removed critical barriers on the clinical path for mRNA technology. Based on this technology, mRNA vaccines for the Zika virus and Middle East Respiratory Syndrome Coronavirus were developed. Following the outbreak of the COVID-19 pandemic, mRNA vaccines encoding the surface protein of the novel coronavirus were developed at a record-breaking pace.

However, before mRNA was established as a universal treatment for both rare and common diseases, there remained a series of challenges to be addressed. To overcome these challenges, scientists are developing a range of new techniques, including optimizing mRNA sequences, creating organ- and tissue-specific lipid carriers, and developing in vivo transdermal delivery systems. The combination of these advancements holds the promise of unlocking the potential of mRNA therapy, extending its application beyond vaccines to treat various types of diseases.