MicroRNAs: Small molecules with big therapeutic potential

MicroRNAs (miRNAs) are small non-coding RNAs of approximately 20–25 nucleotides that regulate gene expression at transcriptional and post-transcriptional levels. They play critical roles in several cellular processes, including cell differentiation, proliferation, apoptosis, and immune regulation. Dysregulation of miRNAs has been associated with numerous pathological conditions such as inflammatory diseases, viral infections, cancers, hematological malignancies, and male infertility. This review aims to summarize the biogenesis and mechanisms of action of miRNAs, highlight current miRNA-based therapeutic strategies and delivery systems, and discuss their therapeutic applications and future clinical potential. A comprehensive literature review was conducted using published articles from scientific databases including PubMed, Scopus, and Google Scholar. Relevant studies focusing on miRNA biogenesis, mechanisms of action, therapeutic strategies, delivery approaches, and disease-specific applications were analyzed. Particular emphasis was placed on studies related to inflammatory disorders, hepatitis C virus (HCV) infection, hematological malignancies, and male infertility. Current advances in miRNA mimic therapy, antimiRs, miRNA sponges, and combination therapies were critically reviewed. MiRNAs regulate gene expression by binding to target messenger RNAs and modulating their translation or degradation. Aberrant miRNA expression contributes significantly to disease progression and pathogenesis. Therapeutic strategies including miRNA mimics are designed to restore downregulated miRNAs, whereas antimiRs inhibit overexpressed miRNAs. Miravirsen, targeting miR-122 in HCV infection, represents a promising example of miRNA-based therapeutics progressing into clinical trials. Emerging therapeutic approaches such as miRNA sponges and combined treatment strategies with siRNAs or conventional drugs may further improve therapeutic efficacy. Various delivery systems, including viral vectors, nanoparticles, and lipid-based carriers, have been explored to enhance miRNA stability and target specificity. However, challenges related to delivery efficiency, off-target effects, toxicity, immune responses, and long-term safety continue to limit clinical translation. MiRNA-based therapeutics have emerged as a promising approach for the diagnosis and treatment of diverse human diseases due to their critical regulatory functions in gene expression. Significant progress has been made in understanding miRNA biology and developing novel therapeutic strategies. Despite encouraging preclinical and clinical findings, several challenges remain regarding safe and efficient delivery, specificity, and therapeutic stability. Continued advancements in delivery technologies and molecular targeting are expected to improve the clinical applicability of miRNA therapeutics in the future.