mRNA researchers awarded 2023 Nobel Prize

The Nobel Prize in Physiology or Medicine 2023 has been awarded to two researchers who were instrumental in helping to curb the COVID-19 pandemic, through their discoveries in mRNA base modifications.

The Nobel Assembly has awarded Hungarian biochemist Katalin Karikó and US immunologist Drew Weissman the Nobel Prize in Physiology or Medicine 2023 for their breakthrough findings in RNA vaccine development. The discoveries by the two Nobel Laureates have revolutionised science’s understanding of how messenger RNA (mRNA) interacts with the immune system.

The discovery was critical for developing effective mRNA vaccines during the COVID-19 pandemic.

While researchers have worked to produce vaccine technologies independent of cell culture, this has been challenging, due to the resource-intensive requirement for large-scale cell culture. As a result, historically, the possibilities for rapid vaccine production in response to outbreaks and pandemics has been limited.

Where the ground-breaking research on mRNA began

In the 90s, Katalin Karikó and Drew Weissman were investigating how different RNA types interacted with the immune system, the Nobel Foundation reported.

The organisation stated that in their research, Karikó and Weissman noticed that dendritic cells recognise in vitro transcribed mRNA as a foreign substance. This leads to their activation and the release of inflammatory signalling molecules. They questioned why the in vitro transcribed mRNA was recognised as foreign while mRNA from mammalian cells did not result in the same reaction.

Nucleoside bases in RNA from mammalian cells are frequently chemically modified, while in vitro transcribed mRNA is not, the Nobel Foundation stated. According to the institution, Karikó and Weissman considered whether the absence of altered bases in the in vitro transcribed RNA could provide reasoning for the unwanted inflammatory reaction.

Karikó and Weissman went onto produce different variants of mRNA, each with unique chemical alterations in their bases. These were then delivered to dendritic cells. The results showed that the inflammatory response was almost eliminated when base modifications were included in the mRNA.

These data were published in 2005, fifteen years before the COVID-19 pandemic, of which mRNA vaccines were instrumental to controlling.

Through the discoveries, Karikó and Weissman opened up opportunity for the pharmaceutical industry to advance mRNA technology. In 2010, several companies were working on developing the method.

Then, when the COVID-19 pandemic broke, two nucleoside base-modified mRNA vaccines encoding the SARS-CoV-2 surface protein were developed at a rapid pace, noted the Nobel Foundation.

Nobel Prize in Physiology or Medicine 2023 Laureates – their important work in mRNA

“Thanks to the pioneering contributions of Karikó and Weissman, nearly 13 billion doses of mRNA COVID-19 vaccines have been administered worldwide,” Dr Gilles Georges, Vice President and Chief Scientific Officer at CAS explained to EPR.

Ultimately, Karikó and Weissman “demonstrated that changing the type of the RNA nucleotides within the vaccine altered the way in which cells see it. This increased the amount of vaccine protein made following the injection of the RNA, effectively increasing the efficiency of the vaccination: more response for less RNA,” stated Professor John Tregoning, Professor in Vaccine Immunology within the Department of Infectious Disease, Imperial College London. “This was a vital building block of the success of the RNA vaccines in reducing disease and death during the pandemic”. 

“Beyond the realm of COVID-19, the agility of the mRNA platform holds immense promise for combating a wide spectrum of infectious diseases, including influenza. It also positions us to be better prepared for any potential future pandemics that may arise… [additionally the] concept of harnessing mRNA in the realm of medicine opens doors to an array of possibilities, including the development of therapeutic vaccines for cancer and innovative mRNA-based therapies for addressing a multitude of genetic disorders,” Dr Georges told EPR.

Katalin Karikó

In 1989, Katalin Karikó was appointed Assistant Professor at the University of Pennsylvania, where she stayed until 2013. Following this tenure, she became Vice President and later Senior Vice President at BioNTech RNA Pharmaceuticals. Since 2021, she has been a Professor at Szeged University and an Adjunct Professor at Perelman School of Medicine at the University of Pennsylvania. She received her PhD from Szeged’s University in 1982.

Drew Weissman

Drew Weissman is the Roberts Family Professor in Vaccine Research and Director of the Penn Institute for RNA Innovations. He established his research group at the Perelman School of Medicine at the University of Pennsylvania in 1997. Weissman received his MD, PhD degrees from Boston University in 1987.

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