New RNA-based active agents have been developed by researchers at Martin Luther University Halle-Wittenberg (MLU) to reliably protect plants against the Cucumber mosaic virus (CMV), the most common virus in agriculture and horticulture. These active ingredients have a broad-spectrum effect, with a series of RNA molecules supporting the plant's immune system in combating the virus. In laboratory experiments, 80 to 100 percent of the treated plants survived an infection with a high viral load, as reported in "Nucleic Acids Research." The journal has selected their paper as a "breakthrough article," and the researchers are working on transitioning the concept from the laboratory to practical applications.
© Uni Halle / Heiko Rebsch
Cucumber mosaic virus is particularly devastating for crops, transmitted by about 90 species of aphids and affecting more than 1,200 plant species, including squash, cucumbers, cereals, and medicinal and aromatic plants. Infected plants are easily identified by a characteristic mosaic pattern on their leaves and fail to thrive, rendering their fruits unsellable. Currently, there are no approved agents against CMV, but the new research from MLU could offer a long-term solution by directing the plant's natural defenses more effectively.
When a virus infects a plant, it uses the plant's cells as hosts, multiplying via its ribonucleic acid (RNA) molecules. These foreign RNA molecules trigger an initial immune response from the plant. Special enzyme scissors recognize and cut the viral RNA molecules, producing small interfering RNAs (siRNAs) that spread throughout the plant, triggering a second immune response. The siRNA molecules bind to special protein complexes, guiding them to the viral RNA molecules, where the proteins break down the harmful RNA into harmless fragments.
"This defense process is generally not very effective, as a viral infection produces many different siRNA molecules, but only a few have a protective effect," says Professor Sven-Erik Behrens from the Institute of Biochemistry and Biotechnology at MLU. His team has developed a method to identify highly efficient siRNA molecules and has combined several into efficient double-stranded RNA molecules (edsRNAs) suitable for use in plants. These edsRNAs act as a "package" that breaks down into siRNAs upon entering plant cells, allowing a large number of effective siRNA molecules to exert a protective, antiviral effect.
The team conducted numerous laboratory experiments on the model plant Nicotiana benthamiana, demonstrating that edsRNA-based active agents reliably protect against CMV. "The plants in our experiments were infected with a very high viral load: all untreated plants died," explains Behrens. In contrast, 80 to 100 percent of treated plants survived. A special advantage of edsRNA agents is that when the package breaks down, it produces efficient siRNA molecules that exclusively target the virus at different sites, significantly increasing the protective effect. "RNA viruses like CMV are dangerous because they evolve rapidly. The genetic material of this virus is made up of three separate parts, which can mix, increasing the chance of new mutations. To achieve maximum protection, our active ingredients target different genome parts," says Behrens. The team has optimized the process of screening for efficient siRNAs and can adapt the procedure to target new viral mutations within two to four weeks. "Time is crucial: when a new virus variant emerges, we can quickly modify the active agent," Behrens explains. The approach may also apply to other pathogens and pests.
Currently, the substances are administered manually in the lab, either by injection or rubbing them into plant leaves. The team is collaborating with pharmacist and drug delivery specialist Professor Karsten Mäder at MLU to make the RNA-based substances more durable and easier to apply, such as by spraying. They are also planning field trials to test the substances under real conditions and are in discussions with companies about future industrial production. Potential new crop protection products must still undergo an approval process, so it will take time before a product to combat CMV enters the market. "However, we are convinced that our approach is feasible. The first crop protection product with an RNA-based active ingredient was recently approved in the USA," says Behrens.
The editors of "Nucleic Acids Research" selected the MLU researchers' paper as a "breakthrough article," a distinction given to only two to three percent of the articles published in the journal each year. Around 1,300 articles appeared in the journal in 2024.
The work was funded by the German Research Foundation (DFG), the Federal Ministry of Education and Research (BMBF), and the state of Saxony-Anhalt.
Source: IDW Online