Overcoming antifungal resistance in Candida albicans via RNA interference: a therapeutic perspective.

Candida albicans remains a significant cause of nosocomial infections, with increasing antifungal resistance posing a global health challenge. Current therapies, including azoles, echinocandins, and polyenes, are increasingly limited by evolving resistance mechanisms such as efflux pump overexpression and ergosterol pathway mutations. This review explores the potential of RNA interference (RNAi) as a novel therapeutic strategy against drug-resistant C. albicans. While RNAi has shown efficacy in other fungal pathogens, its application in C. albicans is still in early stages. We discuss established antifungal targets, introduce emerging RNAi-based gene silencing approaches, and highlight potential molecular targets including ERG1, ERG6, ERG11, CDR1, CDR2, CLB2, and GSC1. RNAi offers a transformative route to overcome resistance at the transcriptional level, bypassing post-translational mutation-related failures of conventional drugs. With advances in small-interfering RNA (siRNA) design, chemical modifications, and nanoparticle delivery systems, RNA-based therapeutics may reshape the future of antifungal treatment.