Inhibition of microRNA function by antimiR oligonucleotides

TLDR

MicroRNAs are critical post‑transcriptional regulators whose dysregulation is linked to many human diseases, making them attractive therapeutic targets and driving the rapid development of computational and experimental tools to study their functions. This review examines antisense oligonucleotides (antimiRs) as loss‑of‑function tools for inhibiting miRNAs. We describe the antisense chemistries used to design antimiRs, common in vivo delivery methods, and approaches for assessing inhibition efficacy and off‑target effects. Recent advances demonstrate that antimiR‑mediated pharmacological inhibition of disease‑associated miRNAs holds great promise for novel miRNA‑based therapeutics.

Abstract

MicroRNAs (miRNAs) have emerged as important post-transcriptional regulators of gene expression in many developmental and cellular processes. Moreover, there is now ample evidence that perturbations in the levels of individual or entire families of miRNAs are strongly associated with the pathogenesis of a wide range of human diseases. Indeed, disease-associated miRNAs represent a new class of targets for the development of miRNA-based therapeutic modalities, which may yield patient benefits unobtainable by other therapeutic approaches. The recent explosion in miRNA research has accelerated the development of several computational and experimental approaches for probing miRNA functions in cell culture and in vivo. In this review, we focus on the use of antisense oligonucleotides (antimiRs) in miRNA inhibition for loss-of-function studies. We provide an overview of the currently employed antisense chemistries and their utility in designing antimiR oligonucleotides. Furthermore, we describe the most commonly used in vivo delivery strategies and discuss different approaches for assessment of miRNA inhibition and potential off-target effects. Finally, we summarize recent progress in antimiR mediated pharmacological inhibition of disease-associated miRNAs, which shows great promise in the development of novel miRNA-based therapeutics.