Katalín Kariko y Drew Weissman they have won the Nobel Prize in Physiology or Medicine 2023 for their discoveries, which have served to develop the Messenger RNA vaccines against COVID-19 from Moderna and Pfizer/BioNtech, as reported today by the Swedish Academy. The work carried out for 40 years by Hungarian biochemist Katalin Karikó has been key to the development of these drugs, and Drew Weissman collaborated with her to make therapies based on messenger RNA possible. The Pfizer or Moderna vaccines would not exist without her contribution.
The jury of the Swedish Academy has highlighted: that this award is granted to Karikó and Wiessman “for their discoveries on nucleoside base modifications that allowed the development of effective mRNA vaccines against COVID-19”, and adds that: “The The discoveries of the two Nobel laureates were instrumental in developing mRNA vaccines against COVID-19 during the pandemic that began in early 2020. Through their groundbreaking discoveries, which have fundamentally changed our understanding of how mRNA interacts with our immune system, the honorees contributed to an unprecedented rate of vaccine development during one of the greatest threats to human health in modern times.”
Both scientists received the Frontiers of Knowledge award from the BBVA Foundation in 2022 for the same research, and in 2021 they were also among those honored with the Princess of Asturias awards. However, Karikó’s first investigations were rejected, and the same thing happened to Weissman. In fact, in an interview with the newspaper The country In December 2020, Karikó stated that no one supported her to make vaccines and therapies based on the RNA molecule and that “she received one rejection letter after another from institutions and pharmaceutical companies when she asked them for money to develop this idea.”
Messenger RNA vaccines demonstrated their potential
“In our cells, the genetic information encoded in DNA is transferred to messenger RNA (mRNA), which is used as a template for the production of proteins,” they explain from the Swedish Academy. In the 90s, Karikó raised the idea of using this messenger as therapy to cure the sick. The scientist’s hypothesis was that, if the appropriate piece of RNA were introduced into the patients’ cells, they would produce the missing protein that causes anemia or generate an immune response against an infection, or even to fight cancer. Immunologist Drew Weissman, for his part, wanted to develop more effective vaccines and also believed that this molecule could be useful in achieving this.
“Karikó and Weissman discovered that making small modifications to the composition of the mRNA decreased reactogenicity and inflammation, and mRNA vaccines began to be applied to humans”
The two scientists began collaborating “focusing on how different types of RNA interact with the immune system.” The first results of their research were published in 2005 – 20 years before the COVID pandemic – and showed that “the inflammatory response was almost abolished when base modifications were included in the mRNA.” Subsequently, they showed that “the base modifications reduced inflammatory responses and increased protein production,” meaning that “they had removed critical obstacles on the path to clinical applications of mRNA.”
Interest in mRNA technology began to increase, and by 2010, several companies were working on its development. When the COVID-19 pandemic broke out, two mRNA vaccines with modified bases encoding the surface protein of SARS-CoV-2 were developed at a record pace and approved in December 2020. This technology can be used to develop vaccines against other infectious diseases and, in the longer term, it could be used to “administer therapeutic proteins and treat some types of cancer,” conclude the experts from the Swedish Academy.
A technology that has saved millions of lives
Carlos Briones, Doctor in Biochemistry and Molecular Biology, CSIC researcher at the Astrobiology Center, where he directs a group that investigates the origin and early evolution of life and the RNA world, explains in statements to SMC Spain that the contribution of these scientists “it was essential for the production of the most efficient vaccines against SARS-CoV-2 during the covid-19 pandemic (those marketed by BioNTech/Pfizer and Moderna), and its use has undoubtedly saved millions of lives around the world.” . In addition, this same methodology is being used for the development of vaccines against other pathogens, and in the treatment of different diseases.”
“This is a more than well-deserved award, which I had opted for this year and which makes me especially happy. Furthermore, the award once again highlights the relationship that exists between basic research and its biotechnological applications, and underlines the importance that RNA (an intermediate biomolecule between DNA and proteins in all our cells) has had in biology since the beginning of research. life on Earth, about 3.8 billion years ago.”
In the opinion of Jose Gomez Rial, immunologist at the University Clinical Hospital of Santiago, The first mRNA vaccines, with the unmodified formulation, were highly reactogenic, with the production of a large number of inflammatory side effects at the local level that made their use unthinkable in humans. It was the work of Karikó and Weissman that discovered that making small modifications in the composition of the mRNA (changing a Uridine for a pseudo-Uridine in the formulation of the nucleosides that make up the mRNA molecule) reactogenicity and inflammation decreased, disappearing local side effects and mRNA vaccines began to be applied to humans.”
“Weissmann and Karikó’s work, academic, impeccable, elegant, focused on a basic research question, has literally saved the lives of millions of people. As José Angel Valente’s poem says, “We don’t know how far or how long a word can reach, in this case, a research work,” he concludes. Jose Alcamivirologist, director of the AIDS Immunopathology Unit (Carlos III Health Institute) and principal investigator of the CombivacS study on heterologous guidelines.