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Revolutionary therapy against deadly fungal infections discovered!
Research at the University of Würzburg is developing innovative siRNA strategies against Aspergillus fumigatus to combat deadly fungal infections.
Revolutionary therapy against deadly fungal infections discovered!
A research team at Würzburg University Medicine has developed a promising new strategy against the opportunistic fungus *Aspergillus fumigatus*. The results, which appear in the journal Nanoscale published show how a combination of small RNA molecules (siRNA) and the antifungal agent amphotericin B in nanoparticles can be used more intensively against this dreaded pathogen.
Aspergillus fumigatus is considered the main cause of serious lung infections, affecting approximately 2 million people worldwide each year. Mortality from invasive infections can be up to 85%, even when treated with conventional antifungals. A combination of increasing fungal resistance to current therapeutic approaches and the fact that no new classes of antimycotics have been approved for over two decades has highlighted the need for new therapeutic approaches. According to the research team's estimates, there were 6.5 million infections worldwide in 2022, resulting in 3.8 million deaths.
Innovative approaches to therapy
The team's innovative method is based on RNA interference (RNAi), a mechanism for targeted gene silencing. For use against *Aspergillus fumigatus*, the researchers package the RNA molecules together with amphotericin B in anionic liposomes. These nanoparticles are crucial because they help overcome the fungus's dense cell wall, which has made previous therapeutic approaches much more difficult.
The study highlights that the siRNA is able to inhibit three key genes that are essential for the growth of the fungus. Initial tests using insect larvae as a model organism show a significant reduction in fungal growth and the effectiveness of the siRNA against *Aspergillus fumigatus*.
A central finding of the publication is that co-loading the siRNA and the antifungal agent into anionic liposomes significantly improves the efficiency of the treatment. Experiments found that siRNA specifically targeting the hapB, hapX and sreA genes showed promising antifungal effects. Treatment with combined siRNA led to a significant delay in the growth of the fungus over a period of ten days.
Challenges and outlook
Despite these advances, researchers are faced with the task of further optimizing the delivery mechanisms for the siRNA. Previous attempts with cationic liposomes and other delivery systems have not been successful. The current work aims to increase effectiveness and incorporate additional molecular targets into the treatment approach.
The results highlight interdisciplinary collaboration and advances in nanomedicine. The study was supported by the German Research Foundation (DFG), which emphasizes the need for innovative therapeutic approaches to combat fungal infections.
The findings presented here could have the potential to fundamentally change existing treatment options for one of today's most dangerous fungal infections and thus offer new hope for affected patients.
The detailed research results and their significance are presented in the work of Yu et al. further in depth, which was published on March 24, 2025 and under the DOI 10.1039/d4nr03225j is accessible.