The 2023 Nobel Prize in Medicine or Physiology goes to Katalin Kariko and Drew Weissmann. for his research related to RNA vaccines against Covid-19, The Nobel Assembly of the Karolinska Institute in Stockholm announced this on Monday.

The Nobel Prize in Medicine is the first in a round of these prestigious awards, which will be announced in the coming days. Physics, chemistry, literature, peace and finally economics next Monday.

In a statement, the Karolinska Institutet noted that the award was given to both of them “for their discoveries in the field of modifications of nucleoside bases, which “has enabled the development of effective mRNA vaccines against Covid-19.”

Discoveries of two Nobel laureates were fundamental to develop effective mRNA vaccines against Covid-19 during the pandemic that began in early 2020.

“With their groundbreaking discoveries that fundamentally changed our understanding of how mRNA interacts with our immune system, the laureates have contributed to “An unprecedented pace of vaccine development during one of the greatest threats to human health of our time.”he pointed.

Katalin Kariko was born in 1955 in Szolnok, Hungary. He received his PhD from the University of Szeged in 1982 and carried out postdoctoral research at the Hungarian Academy of Sciences in Szeged until 1985. He then conducted postdoctoral research at Temple University in Philadelphia and the University of Health Sciences in Bethesda. In 1989, she was appointed assistant professor at the University of Pennsylvania, where she remained until 2013. She then became Vice President and then Senior Vice President of BioNTech RNA Pharmaceuticals. As of 2021, she is a professor at the University of Szeged and an associate professor at the Perelman School of Medicine at the University of Pennsylvania.

Drew Weissman was born in 1959 in Lexington, Massachusetts, USA. He received his MD and PhD degrees from Boston University in 1987. He completed his clinical training at Beth Israel Deaconess Medical Center at Harvard Medical School and conducted postdoctoral research at the National Institutes of Health. In 1997, Weissman founded his research group at the Perelman School of Medicine at the University of Pennsylvania. He is the Roberts Family Professor of Vaccine Research and Director of the Pennsylvania Institute for RNA Innovation.

What is messenger RNA?

In our cellsThe genetic information encoded in DNA is transferred to messenger RNA (mRNA). which is used as a matrix for protein production. In the 1980s, efficient methods for producing mRNA without cell culture, called in vitro transcription, were introduced. This decisive step accelerated the development of molecular biology applications in various fields. Ideas for using mRNA technology for treatments and vaccines were also gaining traction, but there were still hurdles ahead.

In vitro transcribed mRNA was considered unstable and difficult to deliver, necessitating the development complex lipid carrier systems for mRNA encapsulation. Moreover, the mRNA produced in vitro caused inflammatory responses. Therefore, enthusiasm for developing mRNA technology for clinical use was initially limited.

The institute notes that These obstacles did not discourage Hungarian biochemist Katalin Kariko. who has dedicated himself to developing methods to use mRNA for therapeutic purposes. In the early 1990s, when she was an assistant professor at the University of Pennsylvania, she remained true to her vision of using mRNA as a therapeutic despite difficulty convincing research funders of the importance of her project.

Carico’s new colleague at his university was immunologist Drew Weissman. He was interested in dendritic cells, which play an important role in immune surveillance and activation of vaccine-induced immune responses. Inspired by new ideas, soon A fruitful collaboration began between them. focusing on how different types of RNA interact with the immune system.

Kariko and Weisman noticed that dendritic cells recognize in vitro transcribed mRNA as a foreign substance, which leads to its activation and release of inflammatory signaling molecules. They wondered why mRNA transcribed in vitro was recognized as foreign, while mRNA from mammalian cells did not produce the same response. Kariko and Weissman realized that different types of mRNA must differ in some critical properties.

RNA contains four bases, abbreviated A, U, G and C, which correspond to the A, T, G and C in DNA, the letters of the genetic code. Kariko and Weissman knew that the bases of RNA from mammalian cells are often chemically modified, whereas mRNA transcribed in vitro is not. They wondered whether the lack of base changes in RNA transcribed in vitro may explain the unwanted inflammatory response.

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To explore alternatives, produced different variants of mRNA, each have unique chemical changes at their bases that they deliver to dendritic cells. The results were surprising: the inflammatory response virtually disappeared when base modifications were included in the mRNA.

It was paradigm shift in our understanding of how cells recognize and respond to different forms of mRNA. Kariko and Weissman immediately realized that their discovery had enormous implications for the use of mRNA in therapy. These fundamental results were published in 2005, fifteen years before the Covid-19 pandemic.

In additional studies published in 2008 and 2010, Kariko and Weissman demonstrated that delivery of mRNA generated with base modifications It markedly increased protein production compared to unmodified mRNA. The effect was due to a decrease in the activation of an enzyme that regulates protein production. With the discovery that base modifications reduce inflammatory responses and increase protein production, Kariko and Weissman have cleared a major barrier to the clinical use of mRNA.

Interest in mRNA technology began to increase, and in 2010 several companies have worked to develop this method. Vaccines against Zika virus and MERS-CoV were sought; the latter is closely related to SARS-CoV-2.

Since the start of the Covid-19 pandemic, they have grown at a record pace.mRNA vaccines with modified bases encoding the surface protein of SARS-CoV-2.. The protective effect was reported to be around 95%, and both vaccines were approved back in December 2020.

The impressive flexibility and speed with which mRNA vaccines can be developed also paves the way for the use of a new platform. for vaccines against other infectious diseases. In the future, this technology could also be used to deliver therapeutic proteins and treat certain types of cancer.

Other SARS-CoV-2 vaccines based on different methodologies have also been rapidly introduced and together More than 13 billion Covid-19 vaccine doses have been administered worldwide.

Vaccines have saved millions of lives and prevented serious illness in many other people, allowing societies to open up and return to normal conditions. With their fundamental discoveries about the importance of mRNA base modifications, this year’s Nobel laureates have made fundamental contributions to this transformative development during one of the greatest health crises of our time.

The Nobel Assembly, consisting of 50 professors from the Karolinska Institutet., awards the Nobel Prize in Physiology or Medicine. Since 1901, the Nobel Prize has been awarded to scientists who have made major discoveries for the benefit of humanity.

(according to information from EFE and Nobel Prize laureates).