miRNA delivery systems, improvements, and challenges

MicroRNAs (miRNAs) are critical post-transcriptional regulators of gene expression involved in a wide array of physiological and pathological processes. Since their discovery, miRNAs have been recognized for their capacity to modulate diverse gene networks, impacting cell proliferation, differentiation, apoptosis, and metabolism. Their dysregulation is strongly implicated in cancer, cardiovascular, and neurological diseases, making them attractive biomarkers and therapeutic targets. However, miRNA therapeutics face substantial challenges in clinical translation, including instability, degradation, delivery inefficiency, rapid systemic clearance, and off-target effects. To address these, both viral and non-viral delivery systems have been engineered, ranging from lipid nanoparticles and polymers to conjugates and exosomes, to enhance miRNA stability, specificity, and cellular uptake. Advances such as chemical modifications, ligand-mediated targeting, and stimuli-responsive carriers have significantly improved delivery efficacy. Despite notable progress, key obstacles, including tissue penetration, especially across the blood–brain barrier, immunogenicity, and safety, remain. Continued innovation in targeted, responsive delivery technologies is essential to realize the clinical potential of miRNA therapeutics fully.