Self-Destruction of Glioblastoma
With a unique RNA molecule, a team led by researchers from Jülich has successfully targeted and destroyed glioblastoma cancer cells. The so-called selectively expressed RNA (seRNA) induces diseased cells to produce a protein that triggers their own programmed cell death. In healthy cells, the seRNA remains inactive and has no effect. This was demonstrated in mouse studies, the results of which have now been published in Nature Communications. The method is based on a newly developed and easily customizable platform technology. This could provide the foundation for developing a new generation of effective drugs, not only against cancer cells but also against viruses and genetic diseases such as cystic fibrosis. (Source: Forschungszentrum Jülich – Press Release)
In cancer research, the long-standing goal has been to develop medications that target only tumor cells without causing side effects in healthy cells. To achieve this, drugs must distinguish between healthy and diseased cells. Jülich researchers have developed an RNA molecule that is active only in diseased cells, where it leads to the production of therapeutic agents. The new RNA form was then characterized in detail in close collaboration with scientific partners from Cologne, Würzburg, and Strasbourg.
Since the development of COVID-19 vaccines, messenger RNA (mRNA) is no longer unfamiliar. In cells, it reads the genetic instructions encoded in DNA and uses this blueprint to produce various molecules—mostly proteins—required for cellular metabolism.
Jülich researchers have now advanced this principle to create selectively expressed RNA (seRNA). This molecule consists of several components, one of which acts as a highly specific sensor: it detects whether the cell is diseased—for instance, a glioblastoma cell—and binds to one of the tumor-specific mRNAs, such as a cancer marker, forming a double-stranded RNA. The cell interprets this RNA double strand as a potential viral attack. It recognizes the associated threat and partially degrades the seRNA. This activates other components of the seRNA complex, leading to the production of an enzyme that prompts the cancer cell to self-destruct. Depending on the choice of seRNA components, it can be tailored to activate in specific target cells in the body and produce specific therapeutic molecules. In healthy cells, where the cancer marker is absent, no activation occurs, thereby avoiding harm to healthy cells.
mRNA molecules are always active and present in every cell. This is different with seRNA molecules. Their activation occurs only when the green-labeled component of the seRNA (antisense) binds to a specific RNA (target sense RNA) present exclusively in the selected target cell, forming a double strand. This double strand acts as an alarm signal for the cell, triggering a partial degradation of the seRNA. This degradation activates the remaining seRNA, leading to the production of an enzyme. In the case of cancer cells, this enzyme initiates programmed cell death (defined in the illustration by the orange component, the Effector). However, the type of enzyme produced can be freely chosen depending on the application. In healthy cells, the seRNA is not activated because these cells do not contain cancer-specific RNA. This prevents side effects, and the inactive seRNA is completely degraded within a few hours through natural processes.
“Using the cell’s own RNA as a ‘switch’ is entirely novel,” explains PD Dr. Bernd Hoffmann from the Institute of Biological Information Processing, Mechanobiology (IBI-2) at Forschungszentrum Jülich. “And the modular design makes seRNA a highly promising platform technology.” Depending on which mRNA components the seRNA binds to and which proteins it activates, the new method could be applied to various cancers, viral diseases such as hepatitis B, and autoimmune diseases. “With the development of seRNA molecules for medical applications, we can ensure the targeted attack on diseased cells while simultaneously enabling the selective production of therapeutic agents,” says Prof. Rudolf Merkel, Director of IBI-2.
IBI-2 will further develop the switchable seRNA molecule technology under a research contract, optimizing it for use against glioblastoma and other diseases. The new platform technology is now set to undergo preclinical and initial toxicological studies for liver cancer as well. The company SRTD Biotech holds the patent for the seRNA technology.
FZJ/A. Stettien, 08.01.2025
Note: The article has been translated from German to English. It is based on a press release from FZJ.
The original press release can be found at:
Self-Destruction of Glioblastoma
The original publication can be found at (Open Access):
Selectively expressed RNA molecules as a versatile tool for functionalized cell targeting, Nature Communications, by Frederik Rastfeld, Marco Hoffmann, Sylvie Krüger, Patrick Bohn, Anne-Sophie Gribling-Burrer, Laura Wagner, Nils Hersch, Carina Stegmayr, Lukas Lövenich, Sven Gerlach, Daniel Köninger, Christina Hoffmann, Helene L. Walter, Dirk Wiedermann, Hajaani Manoharan, Gereon R. Fink, Rudolf Merkel, Heribert Bohlen, Maria A. Rueger, Bernd Hoffmann, DOI: 10.1038/s41467-024-55547-6
Localization in Helmholtz Information:
Helmholtz Information, Program 2: Natural, Artificial and Cognitive Information Processing, Topic 5: Decoding Brain Organization and Dysfunction
Contact:
Dr. Bernd Hoffmann
Institut für Biologische Informationsprozesse (IBI)
Mechanobiologie (IBI-2)
Forschungszentrum Jülich
Phone: +49 2461/61-6734
E-Mail: b.hoffmann@fz-juelich.de
Contact for this press release:
Dipl. Biol. Annette Stettien
Head of External Communication
Forschungszentrum Jülich
Phone: +49 2461 61-2388
E-Mail: a.stettien@fz-juelich.de
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