News 2023
The power of RNA: making Future Medicines possible today
Later today University College Cork (UCC) will award an Honorary Doctorate to Dr Katalin Karikó for her pioneering messenger RNA (mRNA) research, which led to the BioNTech/Pfizer and Moderna vaccines against COVID-19.
Globally credited with shielding the world from the coronavirus, her academic research has been acknowledged to help turn the tide on the pandemic, with billions of people around the world now protected from the SARS-CoV2 virus.
Dr Katalin Karikó has dedicated her career to achieving a dream that conventional scientific wisdom once deemed implausible. For four decades, her research has focused on the use of mRNA.
DNA contains all the instructions for a cell to grow, function and replicate, and RNA carries out these instructions. Viruses use RNA to store all their genetic information. When a virus forces its RNA into a human cell, the host will use it to make more copies of the virus. mRNA vaccines teach cells how to make a protein that triggers an immune response if someone gets infected.
Photo: Dr Katalin Karikó.
Dr Karikó was convinced mRNA could be used to make their own medicine. She surmounted challenge after challenge until she prevailed, crucially discovering how to overcome the potentially lethal inflammatory response caused by synthetic mRNA that had precluded its use in humans.
Karikó’s relentless allegiance to her goal has prompted a medical revolution. Researchers are exploiting modified mRNAs to develop vaccines for many different disorders ranging from cancers, infectious diseases, autoimmune disorders, heart failure, and inherited illnesses. Irish scientists are also leveraging the power of RNA medicines in a variety of ways leading to a large in increase in research funding and technology transfer.
A strong heritage in RNA research at UCC
UCC has a strong heritage in RNA research, and it is not surprising that RNA medicines form a key strand within our new Future Medicines initiative. UCC Futures - Future Medicines, led by Professor Caitriona O’Driscoll from the School of Pharmacy, combines a multidisciplinary team of renowned world leading scientists, engineers and clinician investigators at UCC and its affiliated hospitals to deliver high-impact, transformational, next generation medicines and medical technologies. It is creating step-change advancements in earlier detection, faster prognosis and targeted treatments to reduce the global health burden and improve quality-of-life for patients with chronic conditions, such as cancer, cardiovascular, gastrointestinal, neurological, and inflammatory diseases.
Photo: UCC Futures - Future Medicines. Advancing translational science into next generation medicines.
One key player is Dr Piotr Kowalski, a current ERC (European Research Council) grant holder at the School of Pharmacy and APC Microbiome Ireland in UCC. Piotr brings extensive knowledge in engineering RNA nanomedicines, and he has significantly contributed to the development of novel biomaterials for mRNA delivery. His current work aims to elucidate the therapeutic potential of a new class of circular RNA molecules.
Photo: Dr Piotr Kowalski, School of Pharmacy and APC Microbiome Ireland, University College Cork.
In addition to Dr Kowalski, a vibrant community in RNA research exists in UCC. Professor John Atkins, Professor Pasha Baranov, Dr Kellie Dean and Dr Martina Yordanova, based in the School of Biochemistry and Cell Biology, have a specific research focus on how RNA is decoded into proteins and how this process is regulated. Professor Atkins founded his research laboratory in UCC in 1981, with a major focus on alternative mRNA decoding mechanisms, such as ribosomal frameshifting that is common in many RNA viruses. In 2021, a team of UCC researchers led by Professor Atkins, together with Swiss collaborators solved the structure of the ribosome during SARS-CoV-2 frameshifting. This information revealed mechanistic aspects of frameshifting that will be useful for the development of antiviral drugs.
Faster access to life changing medicines for patients
Central to the research work carried out by Professor Baranov is the analysis of high throughput data on RNA translation and protein synthesis. The discovery of mechanisms specific to individual genes may provide a means for the development of interventions for modulating their expression. Should these genes be associated with human disease, this information will provide novel drug targets.
Research in RNA Biology continues to grow in the School of Biochemistry and Cell Biology; Dr Kellie Dean is deciphering activities of non-coding RNAs in cancer, and Dr Yordanova’s research aims to identify cell-specific factors influencing decoding of human RNAs. A rapidly growing Cork based start-up company, EIRNA Bio, provides a comprehensive analysis of mRNA translation at genome wide level to major pharmaceutical and drug discovery companies.
Photo: Team of mRNA researchers from the School of Biochemistry and Cell Biology: Professor Pasha Baranov (left), recently appointed Lecturer Dr Martina Yordanova and Senior Research Fellow Dr Gary Loughran.
Professor Pasha Baranov said: “The human genome encodes proteins that play crucial roles in catalysing most chemical reactions in our cells. Correcting a faulty protein or introducing a new one would require modifying the genome, which is challenging and risky. Because mRNA is an intermediate carrier of information from DNA to proteins, its delivery to the cells, enabled by Dr Karikó’s invention, makes it possible to make proteins without introducing permanent changes into our genomes. This provides immense opportunities for medical interventions and health improvements.”
Research in RNA therapeutics has been in the DNA of the School of Pharmacy since its foundation in 2003. RNA-based research in the School of Pharmacy is transnational in nature and is strengthened by close collaboration with experts in RNA Biology, to ensure the clinical advancement of the technology, thus enabling faster access to life changing medicines for patients.
Professor Caitriona O’Driscoll, School of Pharmacy, has over 30 years’ experience in the non-viral delivery of therapeutic nucleic acids. Her research group was the first in the world to describe the synthesis and application of modified cyclodextrins as biomaterials for the delivery of therapeutic nucleic acids/genotherapeutic agents.
The exciting challenge for RNA-based researchers at UCC is to develop RNA medicines for chronic diseases where current treatments have researched a therapeutic ceiling and urgent needs exist to develop new innovative and targeted therapies. This goal is the focus of the UCC Futures – Future Medicines initiative launched in 2022.
Professor O’Driscoll said: “The pioneering work of Dr Kariko has been a step change in the field of non-viral nucleic acid delivery. It has made the therapeutic use of mRNA accessible and acceptable to the industry, the regulators, and the public at large. At the dawn of the UCC Futures – Future Medicines initiative, her visit to UCC is an enormously exciting opportunity for our team in the School of Pharmacy, motivating us to continue the development and expansion of the RNA technology to treat chronic diseases.”
Photo: GeneGut Team, School of Pharmacy, UCC: L-R: Dr Joey O’Shea, Professor Caitriona O’Driscoll, Dr Piotr Kowalski and Dr Patrick O’Dwyer.
Later this afternoon in advance of Dr Karikó’s conferring, she will join this community of RNA researchers for a discussion led by Professor John Cryan, Vice President for Research and Innovation at UCC. It promises to be a rich discussion in a research community that is seeking to improve the lives of patients and develop the next generation of medicines. Live streaming of this event starts on Wednesday 26 April 2023 at 4.15pm.
This strong research history and research focus on understanding RNA virus therapies, the development of interventions for modulating gene expression, and developing RNA medicines for chronic diseases, coupled with the recent launch of UCC Futures – Future Medicines, puts University College Cork in a position to deliver Future Medicines today.