microRNA (miRNA) Therapeutics: From Gene Regulation to Clinical Applications and Future Directions

MicroRNAs (miRNAs) are endogenous, small non-coding RNAs that function as critical post-transcriptional regulators of gene expression, influencing virtually every cellular process. This review provides a comprehensive analysis of the miRNA therapeutics field, beginning with the fundamental biology of miRNA biogenesis and their mechanisms of action in gene silencing. We detail the two primary therapeutic strategies: miRNA inhibition using antisense oligonucleotides (antagomirs) and miRNA replacement using synthetic miRNA mimics. The review critically examines the significant delivery challenges and evaluates current delivery platforms including lipid nanoparticles and GalNAc conjugates (van Rooij & Kauppinen, 2014; Rupaimoole & Slack, 2017). We survey the expanding therapeutic landscape in human medicine, focusing on oncology, cardiovascular, and metabolic diseases (Hanna, Hossain, & Kocerha, 2019). A dedicated section explores the burgeoning field of miRNA applications in veterinary medicine, particularly in cattle and water buffalo, where miRNAs offer revolutionary tools for enhancing production traits (milk yield, meat quality), improving reproductive efficiency, and combating endemic diseases like mastitis and foot-and-mouth disease (Miretti et al., 2013; Ioannidis & Donadeu, 2016). Finally, we discuss challenges in specificity and delivery, while outlining future directions including species-specific design, combination therapies, and the integration of miRNA therapeutics into precision livestock farming. The dual progress in human and veterinary applications underscores miRNAs' potential as transformative therapeutic agents across species.