RNA INNOVATION COMPETENCE CENTRE – supported by Katalin Karikó

RNA INNOVATION COMPETENCE CENTRE supported by Katalin Karikó

Centre of Excellence for Interdisciplinary Research Development and Innovation The Centre of Excellence for Interdisciplinary Research, Development and Innovation (IKIKK) of the University of Szeged is an institution unique in Hungary that brings together and supports the best researchers and projects of the University. We believe that structured information transfer and precise organisational background provide a solid basis for our most outstanding researchers to turn their exceptional ideas into innovative research and market benefits as quickly and efficiently as possible.

The Centre of Excellence for Interdisciplinary Research, Development and Innovation of the University of Szeged is based on clusters that are separated by research disciplines and development areas as defined in the SZTE’s Institutional Development Plan.

The aim of the Life Sciences Cluster, one of the six clusters, is to increase the innovation performance of the University, to enhance the practical use of research results, and to strengthen cooperation between the actors of the R&D and innovation ecosystem in the field of life sciences.

The cluster includes excellent national and international, inter- and multidisciplinary research and projects at the University of Szeged in fields as diverse as translational biomedicine, neurocybernetics, RNA-based innovation development, pharmaceutical and medical technology, agricultural and agro-industrial development, clinical research and biobanking.

llence Centre of Exce linary for Interdiscip lopment Research Deve and Innovation

Life Sciences Cluster

Prof. Dr. Katalin Karikó, Research Professor of the University of Szeged with Dr. Albert Szent-Györgyi, Nobel Laureate of 1937, in front of the Rector’s Office

n RNA Innovatio Competence Center

Direct translation of research results

Albert SzentGyörgyi Me

edical Centre

Prof. Dr. Katalin Karikó, Research Professor of the University of Szeged, with Prof. Dr. László Rovó, the Rector of the University

RNA Innovation Competence Center of the Life Sciences Cluster RNA-based technologies have been the biggest breakthrough in biomedical research in recent years: the application of mRNA-based vaccination and other RNA-based technologies in human medicine will form the basis for many developments in the near future. In order to increase its scientific and development potential, our University has established the RNA Innovation Competence Centre which hosts RNA-based therapeutic developments based on research results in basic research topics related to RNA molecules.

The aim of the Competence Centre is to enable the University of Szeged to effectively participate in the development of the broad application of the RNA-based technologies developed by Dr. Katalin Karikó and Dr. Norbert Pardi and other RNA-based technologies, and to contribute to the development of therapeutic solutions for human diseases with a high public health burden through rapidly translating the research results and developments achieved here into clinical practice.

The RNS Innovation Competence Centre supports the work of researchers and young researchers through the Jessie Stevenson Kovalenko Medal, the Jeantet-Collen Prize and the Novo Nordisk Prize, all of them generous contributions of Prof. Dr. Katalin Karikó.

Generous offers made by Prof. Dr. Katalin Karikó, Research Professor of the University of Szeged Prof. Dr. Katalin Karikó has received numerous professional and social recognitions and awards during the past two years. Some of these included monetary rewards, some of which the alumna of the University offered to her alma mater in order to support the institution’s most outstanding researchers.

The awards whose remunerations were granted to the University are the following: Մ

Jessie Stevenson Kovalenko Medal

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Jeantet-Collen Prize

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Novo Nordisk Prize

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Bolyai János Díj

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Tang Prize in Biopharmaceutical Science 2022

The Competence Centre was started in 2023 with three research groups.

Advancing vaccine and treatment strategies against opportunistic fungal infections Dr. Attila Gácser The research group supported by Professor Karikó’s Novo Nordisk Prize aims to introduce a potentially novel mode of combat against opportunistic pathogenic fungal infections. Specifically, to design, develop, validate, and extensively characterize mRNA-based anti-Candida and anti-Mucor vaccines and/or therapies.

Regarding the social usefulness, the planned research is a priority topic. In the course of the project, a new, internationally unique research group will be created, which, by combining the knowledge acquired in relation to yeasts and filamentous pathogens, working together with the research group of the world’s leading mRNA producer, will be able to find solutions to extremely important problems (i.e., vaccination and mRNAbased therapies against life-threatening fungal infections) from a practical point of view. The research group is working in extensive international cooperation and can be a real catalyst for the cooperation of research groups and enterprises operating in the field of life sciences in the region. The resulting research and development potential and the international cooperation ensure that the research group successfully applies for large, international scientific grants (e.g., ERC, ERA-Net, Horizon Europe, etc.). Implementation of the project can contribute to the efforts to improve the quality of life and increase life expectancy, such developments may have a long-term decreasing impact on the healthrelated costs, which has importance for the health systems and could improve the chances of the patients with serious underlying diseases even in countries with less financial sources.

As a result, we expect to successfully identify and produce efficient anti-C. albicans and anti-M. lusitanicus mRNA vaccine and/or therapie candidates. We further expect to acquire thorough information about their potential mode of action, obtained from complex in vitro characterizations. Thus, due to our full functional preclinical testing, the hereby selected antifungal mRNA-vaccines and mRNA-therapeutic agents might serve as candidates for subsequent clinical characterizations.

Mapping the effect and expression of intravenously administered nucleoside-modified mRNA-LNP in the injured rat spinal cord Dr. Zoltán Fekécs Laboratory of Neuroregeneration has previously successfully used hIL-10 mRNA therapy packaged in lipid nanoparticles (LNP) to treat contusion spinal cord injury, resulting in significant functional and morphological improvement (Gál et al. 2023).

In the project supported by the grant from Professor Karikó’ Jessie Stevenson Kovalenko Medal, the research team is seeking to answer the following questions: 1.

Can the mRNA-lipid nanoparticle complex (mRNA-LNP), when administered intravenously, penetrate the injured spinal cord?

2.

Can monocytes circulating in the blood take up and transport mRNA-LNP into the injured spinal cord?

In the first half of the trial, a control (Th5 contusion + iv. physiological saline; n=6) and an eGFP-mRNA-treated (Th5 contusion + iv. eGFP-mRNA-LNP; n=6) group has been set up. Both groups were treated on the third day post-injury, and on the fourth (n=3) and seventh (n=3) day, eGFP-mRNA expression was mapped in the liver, spleen and injured spinal cord by histo- and immunohistochemistry.

Based on the results obtained so far, intravenously administered eGFP mRNA accumulated predominantly in the liver and spleen and only slightly in the injured spinal cord. To develop an effective intravenous therapeutic route, further modifications are needed to ensure that sufficient mRNA reaches the site of spinal cord injury in a targeted manner.

In the second half of the application, the plan to investigate the possibility of intraperitoneal delivery of eGFP mRNA and intravenous delivery of macrophages transfected with ex vivo eGFP mRNA.

Antitumour siRNA nanocomplexes for nose-to-brain delivery Dr. Gábor Katona Glioblastoma multiforme (GBM) is one of the most aggressive and common types of cancer arising from glial cells with a poor prognosis. Although surgery, chemotherapy, radiotherapy and immunotherapy are used for GBM treatment, the five-year survival rate of patients is less than 5% following diagnosis. Thus, effective treatment of this disease represents one of the greatest unmet medical needs in the field of oncology. Due to the occurrence of the mutations and amplifications in several genes responsible for progression and the aggressive behaviour of GBM cells, small interfering RNA (siRNA) therapy has been proposed as a promising strategy to silence the genes responsible for disease progression, furthermore, to improve the sensitivity of GBM cells towards chemotherapy.

Despite the advantages, the efficiency of siRNA in GBM is limited via its degradation by enzymes and a multitude of obstacles including possible immunogenicity, inefficient cellular uptake, short blood circulation, low blood stability and poor blood–brain barrier (BBB) penetration. However, intranasal drug delivery and nanomedicine may offer solutions to these drawbacks, allowing non-invasive and efficient delivery of drugs to the brain bypassing the BBB, with minimized side effects.

Therefore, our research supported

by Professor Karikó’ Jessie Stevenson Kovalenko Medal aims to develop suitable nanocarrier systems, which is able to protect siRNA from environmental factors (pH or enzymatic degradation) and to facilitate its transport to the target site as well as cellular uptake by tumour cells. There is a good chance that the developed nanoplatforms can be utilized for the efficient delivery of other RNA-based drugs.

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