Professor Jacek Jemielity from the Centre of New Technologies at the University of Warsaw received the 2021 FNP Prize in chemistry and materials sciences for developing chemical modifications of mRNA as tools for therapeutic applications and studies on cellular processes.

Jacek Jemielity was born in 1973 in Wysokie Mazowieckie. He graduated from the Faculty of Chemistry at the University of Warsaw in 1997. He received a Ph.D. degree in 2002 and his habilitation in 2012, both at the same Faculty. He worked at the Department of Biophysics of the Institute of Experimental Physics of the Faculty of Physics at the University of Warsaw. He also gathered research experience at the Institute of Structural Biology in France and the University of Turku in Finland, among other places. He received a full professorship in 2020.

Professor Jemielity specializes in organic and biological chemistry and the biochemistry of nucleotides and nucleic acids. He is the head of the Laboratory of Bioorganic Chemistry at the Centre of New Technologies at the University of Warsaw, in which he leads the research group Jemielity Group. Moreover, he co-founded and heads ExploRNA Therapeutics, a spin-off company of the University of Warsaw, in which the technology of chemically modified mRNA is developed and then used in the design of novel therapies.

Jemielity implemented grants from the National Science Centre and the Foundation for Polish Science (TEAM), among other programs. He co-authored 130 publications for top journals, including Journal of the American Chemical Society, Nature Communications, Chemical Science, and Nucleic Acids Research. These articles were cited more than 2400 times. He is the inventor of solutions protected worldwide by nine patents or patent applications; two of them were bought by BioNTech, four by ExploRNA Therapeutics.

For his achievements, Jemielity received many awards, including the Polityka Science Award for young scientists, the Economic Award of the President of the Republic of Poland, several Awards of the Rector of the University of Warsaw, and he was nominated for the European Inventor Award granted by the European Patent Office.

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Professor Jacek Jemielity is one of the world leaders in research on chemically modified mRNA. The Foundation for Polish Science awarded him for research in this field, namely the development of chemical mRNA modifications.

Messenger RNA (mRNA) is called a cellular recipe for proteins. It is a kind of ribonucleic acid formed in the cell nucleus. As a code fragment copied from DNA, mRNA carries the recipe for building a particular protein. The production of the protein is already the task of ribosomes, which the mRNA seeks after leaving the cell nucleus. Research has shown that appropriately designed mRNA can be delivered to a cell so that the organism can produce a specific protein based on the recipe. This opens the way for work on therapies for a variety of diseases.

An mRNA molecule is a single strand of nucleotides (building blocks of nucleic acids) that ends in a characteristic way on both sides. On one of its ends (the 5?-end) there is a structure called a cap, and on the other end (3?): a polyA tail.

Jemielity conducted many studies of the mRNA cap. Together with his collaborators, he created many molecular tools to study cellular processes related to mRNA such as its degradation and protein biosynthesis initiation. However, the most interesting seemed to be the reagents for modifying mRNA that improve its biological properties, as this research vein holds the most therapeutic potential of such molecules. At the time when Jemielity conducted his first research on mRNA modifications, most of the scientific community was not yet aware of the importance of their later applications in modern biological therapies.

The mRNA molecule is very fragile, degrades quickly, and is very sensitive to various factors and modifications. This is why Professor Jemielity?s research is so important because thanks to the developed analogs (e.g. containing thiophosphate and borate groups in the oligophosphate bridge), mRNA can be much more stable and translationally active. Most importantly, the methods developed by Jemielity and colleagues allow scientists to achieve the desired therapeutic effect with a significantly reduced dose of mRNA, which reduces the risk of side effects.

The mRNA analogs necessary to stabilize this molecule have enabled research in many laboratories around the world. The first generation of Jemielity?s technology for modifying the cap at mRNA?s 5′-end was sold in 2011 to the global biotechnology company BioNTech. Many groups that want to create more stable mRNAs for their medical or biotechnological research seek to work with Jemielity. In later years, he developed two further generations of reagents for mRNA modification, which gave them even more interesting biological properties, significant for therapeutic applications.

The therapeutic use of mRNA remained a very promising technology for many years but was yet to see its first widespread use. The situation changed with the advent of the Covid-19 pandemic when companies very rapidly developed mRNA-based and proved their extreme effectiveness.

The results of Jemielity?s research on developing chemical mRNA modifications are important for the design of many new mRNA-based therapies. Several hundred clinical trials using mRNA are currently underway.

Synthetic mRNA can be used in the creation of therapeutic cancer vaccines, meaning vaccines administered as a drug to people who have cancer. These vaccines are supposed to cause the immune system to better recognize and destroy the cancer. One of the inventions of Professor Jemielity is currently being tested in several clinical trials on therapeutic cancer vaccines.

Another area of mRNA application is antiviral vaccines, which we already witness in their use against the SARS-CoV-2 coronavirus. There are also possible applications in the treatment of genetic rare diseases such as spinal muscular atrophy (SMA), cystic fibrosis, bacterial diseases, or even in regenerative medicine.

 

Photo: prof. Jacek Jemielity_fot. Magdalena Wiśniewska-Krasińska_Archiwum FNP

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