The 2023 Nobel prize in physiology or medicine has been awarded jointly to Katalin Karikó and Drew Weissman for research that was critical in the development of mRNA vaccines against Covid-19.
The Nobel committee honoured Hungarian-born biochemist Karikó and US immunologist Weissman ‘for their discoveries concerning nucleoside base modifications that enabled the development of effective mRNA vaccines against Covid-19’.
Karikó and Weissman started working together at the University of Pennsylvania in the US in the 1990s. While Karikó had been devoted to developing methods to use mRNA for therapy, Weissman was interested in dendritic cells, which have important functions in immune surveillance and the activation of vaccine-induced immune response. Together, they began to focus on how different types of RNA interact with the immune system.
During their collaboration they noticed that an immune response was triggered when they introduced dendritic cells to mRNA produced without cell culture; also known as in vitro transcribed mRNA. They were intrigued as to why in vitro transcribed mRNA triggered this reaction while mRNA from mammalian cells did not and realised that there must be key differences in the properties of the two types.
They knew that the nucleotide bases in RNA from mammalian cells were frequently modified, while the bases in in vitro transcribed mRNA were not and wondered if this could provide an explanation.
To test their theory, they produced different variants of mRNA, each with unique modifications in their nucleotide base sequences, which they then delivered to dendritic cells. They found that in all cases where the mRNA bases had been modified, the immune response was suppressed.
This discovery fundamentally changed understanding of how mRNA interacts with the human immune system. Their findings were published in 2005, 15 years before the start of the Covid-19 pandemic.
In later studies, they showed that, as well as reducing the inflammatory response, mRNA with base modifications also increased protein production due to reduced activation of an enzyme that regulates protein production.
In 2020, at the start of the Covid-19 pandemic, Pfizer–BioNTech and Moderna chose to use mRNA with modified bases to develop their vaccines against the virus, building on the discoveries made by Karikó and Weissmann.
Several other vaccines against Sars-CoV-2, based on different methodologies, were also rapidly introduced, and together, more than 13 billion Covid-19 vaccine doses have been given globally. In addition to Covid-19, mRNA vaccines are being developed for an array of other diseases.
Shortly after the Nobel committee’s announcement, Royal Society of Chemistry president Gill Reid described mRNA vaccine development as ‘a hugely deserving subject’ for the Nobel prize.
‘This recognition for their work is as much about the promise for rapid response to future pandemics and diseases as it is for the impact it had on the global endeavour against Covid-19,’ she added. ‘It’s exciting to see what comes next and how this incredible foundation is built upon by chemical scientists and clinicians around the world.’
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