Title: How mRNA vaccines work and how to improve them with chemical modifications?

Date: 18th June 2021 (Friday)

Time: 12:00 pm (Central European Summer Time)

Host: prof. Joanna Trylska

Virtual seminar: https://us02web.zoom.us/j/89327576237

Meeting ID: 893 2757 6237

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Abstract:

The gene expression process, in which the genetic information from a gene is used in the synthesis of a protein product, controls the function of our organisms. Expression of each protein-coding gene occurs in two crucial steps: (i) copying the information written in DNA to messenger RNA (mRNA) in a process called transcription and (ii) the translation of nucleotide sequence of mRNA into a functional protein. Most of traditional medicines (drugs) exert their therapeutic effect by interacting with proteins in the human body. However, this approach is ineffective in the case of many diseases such as cancer, infectious diseases, and genetic disorders. An alternative to traditional drugs is gene therapy, which is an experimental approach relying on the use of genes to treat or prevent disease. In recent years, synthetic mRNA has emerged as a promising candidate for therapeutic gene delivery. The last decade has brought a significant progress in our understanding of mRNA cellular fate and function and this knowledge has been quickly adopted to improve mRNA-based therapeutics, many of which are currently tested in clinical trials. The great breakthrough in mRNAs-based therapeutic field was the development of mRNA-base SARS-CoV2 vaccines, independently, by BioNTech/Pfizer and Moderna. This success has convinced many that mRNA-based therapeutic interventions and vaccines may soon revolutionize the drug industry.

Our group has developed many reagents providing access to chemically modified mRNAs with improved therapeutic properties. One of our inventions is used in mRNA-based anticancer vaccines that are currently under clinical trials. To identify mRNA modifications with superior properties, we employ an interdisciplinary experimental approach that combines biological chemistry, molecular biophysics, and molecular biology to understand the structure-function relationship for mRNA. We are also aiming at answering one of the ‘big’ still open questions in the therapeutic mRNA field, which is ‘how exactly mRNA translation is controlled in time and space in the cell?’. During the talk, I will provide an overview of our past and recent research focused on either modulating activity of therapeutic mRNA or visualizing the fate of modified mRNA in living cells and whole organisms.