Fungal infections are on the rise globally. According to a study by the Manchester Fungal Infection Group, in 2022, approximately 6.5 million people were infected by a pathogenic fungus, and about 3.8 million died as a result—nearly twice as many as in 2012. Even with medications, known as antifungals, the mortality rate for invasive infections caused by the mold Aspergillus fumigatus is as high as 85%. As resistant fungal strains increase, treatment becomes more difficult, and new therapies are urgently needed.
A research team from Würzburg has succeeded for the first time in packaging small interfering RNAs (siRNAs) with Amphotericin B (AmB) in anionic liposomes to specifically target the dangerous mold fungus Aspergillus fumigatus.
The study, published in the journal Nanoscale and highlighted on the back cover, demonstrates that this RNAi approach shuts down vital fungal genes, thereby inhibiting pathogen growth—a groundbreaking step in the development of new antifungal therapies.
RNAi combined with optimized delivery technology
To specifically target the mold Aspergillus fumigatus, the researchers combined an RNAi approach with optimized delivery technology from nanomedicine. Ribonucleic acid (RNA) plays a central role in the implementation of genetic information. RNA interference (RNAi) acts like a “gene switch,” selectively silencing specific genes. It uses specialized RNA molecules, such as small interfering RNA (siRNA) or microRNA (miRNA), to block genetic instructions needed for protein production.
“Our study builds on the discovery of RNA interference, for which the Nobel Prize in Medicine was awarded in 2006. While siRNA therapies have already been used for genetic diseases, our work is the first successful application of this technology against a human pathogenic fungus in infection models. The genetic differences between fungi and humans offer unique therapeutic opportunities,” explains first author Dr. Yidong Yu from the Center for Experimental Molecular Medicine (ZEMM) and the Department of Medicine II of the University Hospital Würzburg (UKW).
Technological breakthrough in fungal control
One of the biggest challenges was packaging the siRNA in a way that it could penetrate the thick cell wall of the fungus. “The trick was to combine anionic liposomes with small amounts of the antifungal drug Amphotericin B,” reports co-first author Theresa Vogel.
Anionic liposomes are tiny fat vesicles with a negative charge. Amphotericin is a proven antifungal medication that makes the fungal cell walls more permeable, allowing the siRNA to penetrate the fungal cells and specifically inhibit three crucial genes necessary for fungal growth.
The concept was developed by the researchers in close collaboration with Dr. Krystyna Albrecht and Prof. Jürgen Groll from the Institute of Functional Materials in Medicine and Dentistry (FMZ) at UKW, who tested various nanoparticle strategies until the breakthrough was achieved.
Another innovative aspect of the study is the use of insect larvae instead of mice as an infection model to reduce animal testing in mammals. “This work shows how interdisciplinary collaboration enables innovative approaches in nanomedicine,” emphasizes co-senior author Albrecht.
“The results of our study show that this method significantly reduces fungal growth in infection models and, as a proof-of-concept, demonstrates the effectiveness of siRNA as a promising tool against fungal infections in humans,” summarizes senior author Prof. Andreas Beilhack from the Department of Medicine II of UKW.
“The study is particularly significant because infections with Aspergillus fumigatus are increasing globally, and resistance to common antifungals is becoming more common. The siRNA strategy could not only be used against Aspergillus fumigatus but also against other dangerous fungal pathogens.”
Provided by
Universitätsklinikum Würzburg
