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Katalin Kariko - Hungarian creator of mRNA vaccine technology

Hungarian medicine has received international recognition, no doubt thanks to Ignaz Semmelweis and his work. Given the fact that the history of professional Hungarian medicine goes back more than a century and a half, the Hungarian Export Promotion Agency HEPA is working to ensure that the whole world knows as many brands, technologies and products of Hungarian companies with experience in the pharmaceutical industry, in the field of scientific research and developments. Each success achieved by Hungary is a good confirmation of the decisive role that the country plays in medicine and the resulting need to develop new markets. However, all this would not have been possible without such Hungarian doctors, pharmacists and scientists as the Hungarian biochemist Katalin Kariko, who gained worldwide fame for her achievements in the development of mRNA technologies.

Katalin Kariko is a Hungarian biochemist specializing in RNA-mediated mechanisms. Her research included the development of in vitro transcribed mRNA for protein therapy. She was co-founder and CEO of RNARx from 2006 to 2013. Since 2013, she has been associated with BioNTech RNA Pharmaceuticals, initially as Vice President before being promoted to Senior Vice President in 2019. She is also an adjunct professor at the University of Pennsylvania.

Together with colleague Drew Weissman of the University of Pennsylvania, Catalin created the mRNA synthesis technology. Thanks to her, BioNTech, Pfizer and Moderna were able to develop their own coronavirus vaccines, and Kariko and Weissman were among the winners of the prestigious Breakthrough Prize. However, in order to attract the attention of the scientific community to the very idea of ​​​​using mRNA, Kariko needed years of hard work.

Kariko grew up in Kishuysallas, Hungary, in a small house without running water, a refrigerator or a TV. Her father was a butcher and her mother was an accountant. Already in high school, the girl excelled in the natural sciences and showed a clear interest in science. After receiving her doctorate at the University of Szeged, Kariko continued her research and entered the postdoctoral program at the Institute of Biochemistry of the Center for Biological Research in Hungary, and began working in the laboratory of Professor Jeno Tomas, who was engaged in the synthesis of caps - molecular structures at the ends of mRNA. Kariko's dissertation was devoted to the synthesis of oligonucleotides (short lengths of DNA and RNA) and the study of their antiviral effects. Unfortunately, in 1985, the laboratory lost funding, and the young scientist, dreaming of continuing her research, left Hungary for the United States with her husband and two-year-old daughter.

After moving to the United States from 1985 to 1988 as a postdoctoral fellow at Temple University in Philadelphia and the University of Health Sciences at Bethesda in Maryland (1988-1989), Kariko participated in a clinical trial in which patients with AIDS, hematological diseases and with chronic fatigue syndrome were treated with double-stranded RNA (dsRNA). This was considered groundbreaking research at the time, as the molecular mechanism of dsRNA interferon induction was not known, although the antiviral and antitumor effects of interferon were well documented. And in 1989, she was accepted to the University of Pennsylvania, where she worked with cardiologist Elliot Barnathan on messenger RNA. In 1990, while an adjunct professor at the Perelman School of Medicine at the University of Pennsylvania, Kariko submitted her first grant proposal, in which she proposed the creation of an mRNA-based gene therapy. If we talk about the mechanism of work of mRNA (messenger RNA), then it should be understood that messenger RNA (ribonucleic acid) is a kind of “assembly instruction” for proteins. It itself is synthesized in the cell nucleus on the basis of DNA, and then proteins are synthesized in ribosomes on its basis. If we create artificial mRNA with the desired characteristics and then introduce it into the human body, any cell can turn into a factory for the production of certain proteins “on demand”, including antibodies to pathogens, enzymes to stop genetic diseases, and growth factors to repair damaged cells. fabrics. But implementing this technology proved to be difficult.

The mRNA that Kariko and Weissman synthesized had a serious flaw - it caused an immune response that not only destroyed the molecule before it reached the target cell, but could also harm the patient. The researcher was confident that she would figure out how to overcome this obstacle.

“I thought about going somewhere else or doing something else,” she recalls. “I thought maybe I wasn’t good enough, not smart enough. I tried to imagine: here, I have all [the data], I just need to do better experiments.”

Nevertheless, Katalin's perseverance paid off. In 2004, Kariko and Weissman figured out how to prevent a negative reaction in the body. Scientists have noticed that the control group of molecules - transfer RNA (tRNA) - does not cause such a reaction in the body as matrix ones. It turned out that a slight difference in the composition of nucleosides allows evading the immune response of tRNA (nucleosides are part of the nucleotides, from which, in turn, RNA is built): instead of the uridine nucleoside, tRNA contains its isomer (that is, similar in composition, but different in configuration ) pseudouridine. Kariko and Weissman replaced uridine with pseudouridine in their synthetic mRNAs. The new fusion mRNAs no longer elicited an immune response. But then, the technology did not find much response in research circles.

A decade later, it was mRNA synthesis technology that led to the emergence of Moderna: one of its co-founders, the head of the laboratory at Harvard Medical School, Dr. Derrick Rossi, using mRNA, was able to “reprogram” adult cells to behave like stem cells, thus solving the ethical problem of sampling. stem cells.

And only a few years later, when the coronavirus epidemic required the development of new vaccines, synthetic mRNAs came in handy again. Once in the human body, they “force” the cells to produce a spike protein that is part of the virus envelope (it is this protein that makes the virus look like a crown). The immune system attacks this protein and thus "learns" to recognize and neutralize the real coronavirus.