Article Highlight | 3-Oct-2023

In honor of Katalin Karikó's achievements - Biologia Futura special issue

Background stories and a tribute to the research of Katalin Karikó and her colleagues by presenting the latest research by excellent Hungarian researchers

Eötvös Loránd University

As in previous years, the latest Nobel Prizes will be announced between October 2 and 9, 2023. This week is a celebration of science all over the world, when not only the winners, but also the specific field of science becomes the focus of interest. The only solution to humanity's many challenges is the creation of a knowledge-based society, therefore it is essential to properly interpret scientific results and involve different groups of society in the process of common thinking.

The latest issue of the scientific journal Biologia Futura, published jointly by Akadémiai Kiadó and Springer, pays tribute to the research of Katalin Karikó and her colleagues by presenting the latest research by excellent Hungarian researchers.

The fire of research: Katalin Karikó’s legacy

Amid the onset of the COVID-19 pandemic, the world, along with the global scientific community, became acquainted with her ground-breaking work and invaluable contributions to the development of nucleoside-modified mRNA-based COVID-19 vaccines, which have saved countless lives. The latest volume of Biologia Futura showcases a series of papers that exemplify the diversity of RNA-related research in Hungary.

Pseudouridylation, one of the most prevalent RNA modifications in eukaryotes, carries profound significance. Its absence or impairment can lead to severe hereditary diseases. In their paper, Tália Magdolna Keszthelyi and Kálmán Tory provide a comprehensive summary of human genetic disorders linked to damaged proteins within the pseudouridylation process.

Over the course of evolution, microRNAs have evolved into an endogenous regulatory network intricately fine-tuning gene expression in eukaryotes. This complexity arises from the fact that the microRNA gene locus does not produce a discrete gene product but rather a population of small RNAs. In his review, Tamás Orban highlights recent research demonstrating the pivotal role of this regulatory mechanism in cell physiology. He emphasizes that the intricate regulatory complexity inherent in the ‘RNA world’, as an evolutionary legacy, not only manifests in contemporary living cells but also plays a prominent role.

While the etiologies of cancer and COVID-19 are inherently distinct, Edit Oláh explores the unexpected parallels that have emerged between the two. These parallels have proven invaluable in the diagnosis of COVID-19, the development of RNA-based vaccine therapies, and the care of oncology patients who are particularly susceptible to infection. Moreover, ongoing advancements in vaccine development and our deepening understanding of its underlying mechanisms suggest its applications in many medical domains, including oncology.

For decades, the existence of post-transcriptional modifications of RNA nucleotides has been acknowledged. However, determining the precise positions of these modifications and their physiological functions has remained elusive until recent times. Thanks to technological breakthroughs like high-throughput next-generation sequencing (NGS) methods and nanopore-based mapping technologies, we have a growing understanding about the role of such modifications during animal development. Renáta Hamar and Máté Varga summarize these findings, emphasizing how these revelations can impact various facets of development, ranging from fertilization to differentiation, across multiple species.

Ernő Duda poses a thought-provoking question: How much (evil) intelligence can be encoded within a 30 kb virus genome? This inquiry delves into the prolonged coevolutionary dynamics that have honed the virus's ability to evade host protective mechanisms and create molecular mimicry patterns. The new coronavirus, in particular, appears to be a formidable adversary, skillfully exploiting our own defense mechanisms to inflict severe symptoms, often with fatal consequences.

Theoretical frameworks initially assumed that pathogens would inevitably evolve towards reduced virulence. However, empirical observations deviated from this theoretical prediction, giving rise to new theories, with the transmission–virulence trade-off hypotheses emerging as a prominent concept. These hypotheses propose an intermediate level of virulence as the eventual evolutionary outcome. Ádám Kun and his research group highlight the challenges in predicting the short- or long-term evolution of COVID-19's virulence. They point out that a higher viral load does not necessarily equate to a higher risk of death, immunity may not be long-lasting, other hosts can serve as reservoirs for the virus, and viral infection-induced mortality does not necessarily shorten the infectious period.

Genomic epidemiology has now become a foundational element in investigating disease spread during outbreaks and in preparing for emerging zoonotic diseases. Safia Zeghbib, Gábor Kemenesi and Ferenc Jakab trace the development of methods and protocols used in responding to zoonotic diseases, ranging from smaller outbreaks of the severe acute respiratory syndrome (SARS) to the global pandemic triggered by the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019. They summarize the advantages and limitations of relying on genomic epidemiology and underscore the challenges of equitable access to these tools worldwide, particularly in less economically developed countries.

Krisztina Pálóczi, Edit I. Búzás, and András Falus delve into the question of whether exportin-1 (XPO1)-mediated nuclear export of RNAs contributes to the heterogeneity of extracellular vesicles—membrane-enclosed subcellular structures released by various cell types. Their findings expand our understanding of extracellular vesicle heterogeneity, demonstrating that the RNA cargo varies depending on factors such as the size-based category of the vesicles, the cell type releasing them, the functional state of the cells, and the exportin-1-mediated nuclear export of RNAs.

The mRNA vaccine platform pioneered by Katalin Karikó and her colleagues stands as a remarkable testament to innovation. Csaba Deák, Norbert Pardi, and Ádám Miklósi trace the development of mRNA-based therapy, from initial animal models to the first clinical trials. The history of mRNA research began with the elucidation of its role in protein synthesis, ultimately leading to the ground-breaking mRNA vaccine technology. Karikó's pivotal innovation involved the incorporation of modified nucleosides into mRNA, reducing its immunogenicity. Her story imparts valuable lessons, including the influence of market demand as a catalyst, the role of emerging technologies, the significance of universities and academic institutions in fostering innovation, the importance of persistence and faith, and the role of serendipity.

All papers can be found open access, here:
https://link.springer.com/journal/42977/volumes-and-issues/74-1

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