Self-Destructing Cancer Cells: Cutting-Edge RNA Breakthrough
Jülich scientists use novel RNA technology to selectively switch off tumours in the brain.
An Adaptable Platform Technology That Destroys Glioblastoma Cancer Cells
Using a special RNA molecule, a team led by Jülich scientists has specifically attacked and destroyed glioblastoma cancer cells. The so-called selectively expressed RNA (seRNA) causes the diseased cells to produce a protein that leads to their own programmed cell death. In healthy cells, the seRNA remains inactive and has no effect. This was the result of mouse studies, the results of which have now been published in Nature Communications. The method is based on a newly developed and easily adaptable platform technology. This could now form the basis for developing a new generation of effective drugs not only against cancer cells, but also against viruses and genetic diseases such as cystic fibrosis.
Treatment That Distinguishes Between Healthy and Diseased Cells
In cancer research, the goal has long been to develop drugs that only attack tumor cells and do not cause side effects in healthy cells. The active ingredients must therefore be able to distinguish between healthy and diseased cells. Jülich scientists have developed an RNA molecule that only becomes active in diseased cells and leads to the production of active ingredients there. The new form of RNA was then characterized in detail in close cooperation with scientific partners from Cologne, Würzburg and Strasbourg.
Working of mRNA and seRNA in Cells
Since the development of a vaccine against Covid-19, messenger RNA (mRNA) has become well known. In cells, it is responsible for reading the genetic message of DNA and using this blueprint to start the production of various molecules – mostly proteins – that are needed in cell metabolism.
A Novel Approach: Selectively Expressed RNA (seRNA)
Jülich researchers have now developed this principle further into a selectively expressed RNA (seRNA). This is made up of several building blocks. An important building block is a type of highly specific sensor: it detects in the cell whether it is a diseased cell, for example a glioblastoma cell, and combines with one of the tumor-specific mRNAs, for example a cancer marker, to form a double-stranded RNA. The cell assesses this double-stranded RNA as a possible viral attack. The cell recognizes the associated danger and then partially breaks down the seRNA. This activates the other subsequent building blocks of the seRNA complex, which leads to the production of an enzyme that causes the cancer cell to destroy itself. Depending on the choice of seRNA building blocks, it can be individually determined in which target cell of the body the seRNA is activated and which medically effective molecule is produced. In healthy cells, on the other hand, nothing happens due to the lack of the cancer marker. The attack on healthy cells can thus be avoided.
The Modular Design of seRNA for Diverse Applications
“Using the cell’s own RNA as a ‘switch’ is completely new,” explains PD Dr. Bernd Hoffmann from the Institute for Biological Information Processes, Mechanobiology Division (IBI-2) at the Jülich Research Center. “And the modular principle makes seRNA a promising platform technology.” Depending on which mRNA building blocks the seRNA binds to and which protein production it activates, the new method can be used for various types of cancer, viral diseases such as hepatitis B, and also autoimmune diseases. “By developing seRNA molecules for medical applications, we can ensure the targeted attack of diseased cells and at the same time combine this with the selective production of active substances,” says Prof. Rudolf Merkel, Director of the IBI-2.
The IBI-2 will further develop the technology of switchable seRNA molecules as part of a research contract and optimize it for use against glioblastoma and other diseases. The new platform technology will now also go through the pre-clinical phase and initial toxicological studies against liver cancer. The company SRTD biotech is the patent holder for the seRNA technology.
Expert Contact Dr. Bernd Hoffmann
Institute of Biological Information Processes, Mechanobiology Division (IBI-2) E-Mail:b.hoffmann@fz-juelich.d Phone Number: 02461 616734
Original Publication 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, Redmond P. Smyth, Maria A. Rueger & Bernd Hoffmann Journal: Nature Communications Article Title: Selectively expressed RNA molecules as a versatile tool for functionalized cell targeting Article Publication Date: 06 January 2025 DOI: 10.1038/s41467-024-55547-6
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