Inhibition of microRNA function by antimiR oligonucleotides

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.

Antisense Oligonucleotide Treatment Enhances the Recovery of Acute Lung Injury through IL-10–Secreting M2-like Macrophage-Induced Expansion of CD4+ Regulatory T Cells

“…Accumulating evidences suggested that targeting disease-associated miRNAs might be a potential therapeutic strategy for clinical disease, including tumor and inflammatory disease (50)(51)(52). Recently, miR-155, a distinct miRNA molecule, was found to have an important role in inflammatory and immune response (17,19).…”

Pygmy MicroRNA: Surveillance Cops in Therapy Kingdom

“…Researchers have shown that miR-208 inhibition by a locked nucleic acid (LNA) modified anti-miR could potentially protect rats from induced heart failure and hypertension (103). Currently, dose-dependent experiments are at the preclinical stage, to reduce cardiac toxicity (104)(105).…”

Is Use of Micro-RNA–Containing Food Feasible?

“…The first miRNAs discovered in Caenorhabditis elegans by Victor Ambros and Gary Ruvkun [1] were Lin-4 and let-7. Lin-4 negatively regulates the level of LIN-14 protein by imperfect complementary base pairing with the 3'UTR of the Lin-14 mRNA.…”

“…The mature miRNAs are retained in the RNA-induced silencing complex (RISC) and bind to the 3'-untranslated region (UTR) of target mRNAs to regulate expression. Subsequently, miRNAs regulate mRNA expression by inducing degradation or translational repression [1][2][3][4][5][6][7][8].…”