RNA interference and nanomedicine work together to combat dangerous fungal infections

Fungal infections are on the rise worldwide. In 2022, about 6.5 million people were infected with the pathogenic fungus, resulting in about 3.8 million people who died twice as many times as in 2012. As resistant fungal strains increase, treatment becomes more difficult and new treatments are urgently needed.

The Würzburg research team was the first successful in packaging the anionic liposome amphotericin B (AMB) with small interfering RNA (siRNA), targeting the dangerous fungal bacteria Aspergillus fumigatus.

Published in the journal Nanoscale and highlighted in the backcover, this study shows that this RNAi approach shuts down important fungal genes and thereby inhibits pathogen growth.

Combined with RNAi and optimized delivery technology

To specifically target the fungus Aspergillus fumigatus, researchers combined an RNAi approach with optimized delivery techniques from nanomedicines. Ribonucleic acids (RNAs) play a central role in the implementation of genetic information. RNA interference (RNAI) acts like a “gene switch” that selectively silences a specific gene. Special RNA molecules such as small interfering RNA (siRNA) and microRNA (miRNA) are used to block the genetic instructions required for protein production.

“Our research is based on the discovery of RNA interference, which was awarded the Nobel Prize in Medicine in 2006. Although siRNA therapy has already been used in genetic diseases, our study is the first successful application of this technology to human pathogenic fungi in infection models (ZEMM) and Würzburg (UKW), Faculty of Medicine at University Hospital.

Technical breakthroughs in fungal control

One of the biggest challenges was packaging the siRNA in a way that could penetrate the thick cell walls of the fungus. “The trick was to combine anionic liposomes with a small amount of the antifungal amphotericin B,” reported co-author Theresa Vogel.

Anionic liposomes are small, negatively charged adipose vesicles. Amphotericin is a proven antifungal drug that makes the walls of fungal cells more permeable, allowing siRNA to penetrate fungal cells and specifically inhibit three important genes required for fungal growth.

This concept was developed in close collaboration with Dr. Krystyna Albrecht and Jürgen Groll of the Institute for Medical and Dental Materials (FMZ) in UKW.

Another innovative aspect of this study is the use of insect larvae instead of mice as an infection model to reduce animal testing in mammals. “This work illustrates how interdisciplinary collaboration enables innovative approaches in nanomedicine,” stresses co-author Albrecht.

“The results of our study show that this method significantly reduces fungal growth in infection models and demonstrates the effectiveness of siRNA as a promising tool against fungal infections in the UK as a proof of concept.”

“This study is particularly important as the global increase in infections in Aspergillus fumigatus and resistance to common antifungal properties is becoming more common. The siRNA strategy can be used not only against Aspergillus fumigatus, but also against other dangerous fungal pathogens.”