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Next generation therapeutics: are chemically modified mRNAs the greatest hope for gene therapy? Joanna Kowalska (University of Warsawi)

DNA is like a code in which, with the help of well-arranged chemical compound called nucleotides, nature has encoded how organisms function, look, and what are they made of.

The process of using this code to synthesize proteins to control the functioning of the body is called gene expression. Gene expression consists of two key steps. First, the information stored in a relevant piece of DNA (gene) is copied onto messenger RNA (mRNA), which is called transcription. Then, in a process called translation, the mRNA nucleotide sequence is translated into the sequence of amino acids that make up a functional protein.

Most traditional drugs exert their therapeutic effects by interacting with proteins in the human body. This approach is unfortunately ineffective for many diseases, such as cancer, infectious diseases, and genetic disorders. An alternative in such cases is gene therapy.

This is an experimental approach that tries to use genes to treat or prevent disease.

Synthetic mRNAs are used to deliver such therapeutic gene sequences to cells.

The last decade has brought significant advances in understanding the fate and function of mRNA in the cell. Thanks to this knowledge, better gene therapies have been developed and are currently in clinical trials. This includes the development of a vaccine against SARS-Cov2.

Increasingly, the literature suggests that mRNA-based therapeutic interventions and vaccines may soon revolutionize the pharmaceutical industry.

Our group has developed a number of reagents providing access to chemically modified mRNAs with improved therapeutic properties. One of our inventions is used in mRNA-based cancer vaccines that are currently in clinical trials.

In order to identify modifications that give synthetic mRNA better properties, we use an interdisciplinary experimental approach that combines biological chemistry, molecular biophysics and molecular biology. Our research is aimed at understanding the relationship between the structure and function of mRNA.

How exactly is mRNA translation controlled over time and space in a cell?

During the lecture, I will present an overview of our past and recent research focused on studying the therapeutic efficacy of mRNA or visualizing the fate of modified mRNA in living cells and whole organisms.

Dr. Joanna Kowalska's laboratory at the Faculty of Physics of the University of Warsaw conducts interdisciplinary research in the field of nucleic acids.

They are focused on uncovering new functions of nucleotides, oligonucleotides, and nucleic acids in the cell and using this knowledge to create new molecular tools or experimental therapeutics.

The team consists of assistant professors, doctoral students and technical staff. The team works closely with the team of prof. Jacek Jemielity from the Center of New Technologies at the University of Warsaw (CeNT UW).

The group designs reagents for nucleic acid modification, creates molecular probes to investigate nucleotide-related processes, and inhibitors of various nucleotide-related processes.

The research encompasses the chemical or chemoenzymatic synthesis of nucleotide and nucleic acid analogs, and studying their interaction with proteins and enzymes in vitro and in living cells via a wide range of biophysical and biochemical methods, including absorption and emission spectroscopy, nuclear magnetic resonance of small molecules and proteins, X-ray crystallography, mass spectrometry, microscale thermophoresis, and fluorescence microscopy.

The group dealing with gene therapy includes: Joanna Kowalska, PhD, DSc, Marcin Warminski PhD, Anais Depaix PhD, Dorota Kubacka PhD from the Department of Biophysics, Institute of Experimental Physics, University of Warsaw, and prof. Jacek Jemielity PhD DSc, Pawel Sikorski, PhD and Adam Mamot, MA from CeNT UW.

October 17, 2020 at 4.00pm

Auditorium of Faculty of Physics, University of Warsaw

Credits:

Created with an images by Joanna Kowalska