https://www.epo.org/en/node/jacek-jemielity-joanna-kowalska-edward

Jacek Jemielity, Joanna Kowalska, Edward Darżynkiewicz and team

Stabilising messenger RNA

Poland

Finalists for the European Inventor Award 2018

The discovery of more stable messenger ribonucleic acid (mRNA) compounds by a group of Polish researchers paves the way for new therapies for cancers and inherited genetic diseases. Jacek Jemielity, Joanna Kowalska, Edward Darżynkiewicz and their team invented the so-called beta-S-ARCA and beta-B-ARCA compounds that are now finding their way into vaccines and anti-cancer medications.

Thanks to research spanning nearly four decades, the Polish scientists have injected fresh vigour into the field of protein biosynthesis for personalised medicine with their methods for stabilising mRNA.

Their more stable mRNA is not a treatment itself but offers an improved delivery system for therapies using the body's genetic communication channels (its mRNA). The patented invention enables delivery of modified mRNA that can withstand the human body's enzymes. The more stable mRNA is five times more effective and lasts three times longer within a cell than naturally occurring mRNA molecules.

Societal benefit

While survival rates for cancer have greatly improved over the past decade, treatment of the disease can take a heavy toll on patients, especially because of the side effects of chemotherapy. With projections that two out of every five people can now expect to get cancer in their lifetime, personalised medicine could be key to saving lives.

The therapeutic potential of mRNA opens up the possibility of "programming" the human immune system to produce proteins to help fight specific diseases without directly altering a patient's DNA - so far a relatively risky and difficult endeavour. The team's invention may prove to be a powerful asset as scientists unlock the full potential of human DNA. Currently, more than 1 800 disease genes have been identified and more than 2 000 genetic tests have become available, yet there are a total of 20 000 genes in the human genome.

Economic benefit

The scientists at the University of Warsaw (UW) were ahead of the curve in researching more stable forms of mRNA as a vehicle for therapeutics: their research extends back to the 1980s. After discovering promising mRNA compounds, their findings were confirmed, and the invention refined, by a team at Louisiana State University Health Sciences Centre, USA, led by Prof Robert E. Rhoads and Dr Ewa M. Grudzian-Nogalska. They filed for key European patents for mRNA technology in 2008 and established a partnership with German biopharma company BioNTech to bring their patented mRNA stabilisation method to market.

Clinical trials began in 2010, and in the following years BioNTech went on to license mRNA technology to major pharmaceutical companies, including French multinational Sanofi and Swiss multinational Roche's US-based Genentech. Joining forces with Genentech, BioNTech is testing the technology as a stand-alone treatment, as well as in combination with Roche's anti-cancer drug Tecentriq.

According to experts at Market Research Future, the global personalised medicine market is expected to reach EUR 72 billion by 2022, more than doubling in value from EUR 32 billion in 2015. North America is leading the market, followed by Europe. The main drivers are increased patient involvement in healthcare, integrated data from a wider range of sources, integration of wireless technologies with portable healthcare devices and an increase in genetic diseases.

How it works

DNA contains the thousands of genes that provide the instructions for producing the many proteins, enzymes and other molecules that make up the human body. These instructions are passed to the cells' protein factories, ribosomes, through a short-lived instructional code, mRNA. Should DNA become altered through inherited or externally caused mutations, it can send out faulty instructions. In the case of a cancer, this leads to abnormal cell grow. For other genetic diseases, it might result in over- or underproduction of specific proteins.

The mRNA developed by Jemielity and his team alters just one of the roughly 80 000 atoms in a typical mRNA molecule to make it strong enough to withstand enzymes in the body that would otherwise break it down before it could deliver "corrected" genetic instructions.

In one application of the technology, BioNTech has developed a melanoma cancer vaccine that relies on DNA sequencing of a patient's tumour and cross-comparison of this DNA with that of healthy tissue. After mutations are identified, artificially altered mRNA is injected into the patient, allowing the body's immune system to identify and destroy cancer cells with the telltale mutation markers throughout the body. The vaccine has shown promising results in phase one clinical trials.

The inventors

The senior member of the team, Edward Darżynkiewicz, received his PhD from UW in 1976 and has served as a full professor in physics there since 2009. He heads the university's Gene Expression Laboratory and the Interdisciplinary Laboratory of Molecular Biology and Biophysics. In 2015, he was awarded the Leon Marchlewski Medal for outstanding achievements in the fields of biochemistry and biophysics. He has co-authored 208 scientific publications and been named on three European patents and one US patent.

Jacek Jemielity has served as professor of bio-organic chemistry at the Centre of New Technologies, UW, since 2013, and now heads the Laboratory of Bioorganic Chemistry there. He is the author of three European patents and nearly 100 scientific publications. He has been honoured with the UW Rector's Award for his scientific achievements as well as the UW Faculty of Physics Award.

Joanna Kowalska has been an assistant professor in the Division of Biophysics, Faculty of Physics, UW, since 2011. She currently also works as a project leader and has authored more than 50 scientific works and three European patents. She has received the UW Rector's Second-Degree Award, the UW Faculty of Physics Award and the Prof. Pieńkowski Award.

Jemielity, Kowalska, Darżynkiewicz and team received the Economic Award of the President of Poland in 2017 in the "Research & Development" category for their inventions.

Did you know?

The UW team's discovery of robust endings for mRNA molecules that could revolutionise protein biosynthesis and lead to next-generation therapeutics means that they join other European Inventor Award finalists and winners honoured for their work involving mRNA molecules. The UK/Australian team of Jason Chin and Oliver Rackham developed ways of using the genetic information transfer from mRNA to tRNA to re-engineer protein synthesis (2012; Research - finalists). German biochemist Thomas Tuschl found a method to silence mRNA and protein production and thus laid the foundation for many promising therapies (2014; Research - finalist).