ABSTRACT

In the fight against persistent and resistant biofilm-associated infections, which present major difficulties in clinical settings because of their exceptional resistance to antibiotics and immune responses, microRNA (miRNA)-based therapeutics represent a promising new frontier. Complex microbial communities called biofilms, which are encased in extracellular matrices that the body produces on its own, are linked to chronic diseases like non-healing wounds, implant infections, and lung infections caused by cystic fibrosis. By targeting important bacterial genes involved in matrix synthesis, quorum sensing, and resistance mechanisms, certain miRNAs, such as human-derived miR-let-7b-5p, can impair biofilm formation and increase bacterial sensitivity to drugs, according to recent research. In order to diminish biofilm building and impede virulence pathways, miRNAs attach to bacterial mRNAs and either limit translation or promote RNA degradation. Additionally, miRNAs can influence host-bacterial interactions and disrupt bacterial stress responses by acting across kingdom boundaries. Clinical translation is hampered by issues such immune activation, off-target effects, miRNA stability, and effective administration, despite their therapeutic potential. These problems are intended to be addressed by developments in extracellular vesicles, nanocarriers, and biomaterial-based delivery systems. To eliminate biofilms and reduce antibiotic resistance, miRNA therapy can be used in conjunction with currently available antimicrobials. In addition to advancements in delivery systems for stable and site-specific administration, future initiatives will concentrate on creating tailored, focused strategies that use bioinformatics and AI for exact intervention. All things considered, miRNA therapies have revolutionary potential for precision medicine in the treatment of persistent infections linked to biofilms; nevertheless, more interdisciplinary research is necessary to ensure their safety and practical relevance.