MicroRNAs (miRNAs) are ~19–25-nt post-transcriptional regulators whose dysregulation promotes hallmark cancer traits and therapy resistance. This review synthesizes translational principles for developing miRNA therapeutics in oncology, integrating miRNA biology and target engagement with delivery design and clinical experience. We summarize key determinants that shape efficacy and safety, including sequence and chemistry choices, biodistribution and intracellular delivery, dosing strategy, and biomarker-informed patient selection. We compare the main therapeutic modalities, miRNA mimics and inhibitors, and evaluate leading delivery approaches relevant to cancer, including lipid-based systems, polymer-based carriers and conjugates, and extracellular vesicle-inspired platforms, highlighting trade-offs in stability, specificity, immune activation, and tumor exposure. Early clinical programs such as MRX34, TargomiR/MesomiR-1, and cobomarsen, together with experience from non-oncology indications, illustrate both opportunities and practical constraints on tolerability and regimen optimization. We conclude with pragmatic priorities for the field, including standardized analytics for isoforms and target engagement, PK/PD- and biomarker-guided dose selection, and rational combination strategies to safely integrate miRNA-based interventions into precision oncology.
Vélez-Slimani et al. (Wed,) studied this question.