Clinical applications of microRNAs

microRNA (miRNA)-mediated gene regulation is an important mechanism for the development and maintenance of all multicellular organisms. Therefore, miRNA dysregulation may cause changes in the genetic program of cells and leads to diseases. miRNAs target multiple mRNA transcripts by Watson–Crick base pairing patterns to repress the expression of several proteins consequently altering biological pathways and cell functions. Thus, they are becoming an attractive bioagent for novel therapeutic approaches. Technological advances in oligonucleotide synthesis, delivery, chemical modification, and medicinal chemistry are now permitting a rational design and manipulation of oligonucleotides sequences to interfere with the flow of genetic information in order to restore “healthy” genetic programs dysfunctional in human diseases. miRNA therapeutics can be defined mainly by two distinct modes of action: miRNA inhibition or miRNA replacement. Single-stranded antisense oligonucleotide sequences can be used to inhibit miRNA function (antagomir) while double-stranded sequences can replace functional duplex miRNAs (miRNA mimics). In this review, we present key concepts and knowledge gaps in miRNA biology, miRNAs in diseases, and miRNA in clinical applications. Moreover, we provide an overview of current miRNA therapeutics and then discuss the challenges of determining the most effective therapeutic approaches to safely deliver the antagomirs or miRNA mimics with reduced off-target effects. Finally, we envisage future directions to build comprehensive miRNA interactomes and uncover the full spectrum of regulatory rules that can be applied in the rational designing of miRNA therapeutics with higher efficiency and reduced toxicity and side effects.