Anti-miRNA oligonucleotides: A comprehensive guide for design

RNA Biol. 2018 Mar 4;15(3):338-352. doi: 10.1080/15476286.2018.1445959. Epub 2018 Mar 23.

Abstract

MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression post-transcriptionally. As a consequence of their function towards mRNA, miRNAs are widely associated with the pathogenesis of several human diseases, making miRNAs a target for new therapeutic strategies based on the control of their expression. Indeed, numerous works were published in the past decades showing the potential use of antisense oligonucleotides to target aberrant miRNAs (AMOs) involved in several human pathologies. New classes of chemical-modified-AMOs, including locked nucleic acid oligonucleotides, have recently proved their worth in silencing miRNAs. A correct design of a specific AMOs can help to improve their performance and potency towards the target miRNA by increasing for instance nuclease resistance and target affinity. This review outlines the technologies involved to suppress aberrant miRNAs. From the design strategies used in AMOs to its application in novel miRNA-based therapeutics and detection methodologies.

Keywords: AMO design; anti-miRNA; chemical modifications; miRNA; miRNA detection methods; therapeutics.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Clinical Trials as Topic
  • Drug Design
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • MicroRNAs / antagonists & inhibitors*
  • Models, Molecular
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Oligonucleotides / chemistry*
  • Oligonucleotides / pharmacology
  • Oligonucleotides / therapeutic use

Substances

  • Antineoplastic Agents
  • MicroRNAs
  • Oligonucleotides
  • locked nucleic acid

Grants and funding

This work was financially supported by 1. The European Regional Development Fund, through COMPETE2020 — Operational Program for Competitiveness and Internationalization, and the Portuguese Foundation for Science and Technology [grant number POCI-01-0145-FEDER-006939 - UID-EQU/00511/2013, and POCI-01-0145-FEDER-007274 - PEst-C/SAU/LA0003/2013]; 2. Ipatimup integrates the i3S Research Unit, i3S and iBiMED Research Units are partially supported by the Portuguese Foundation for Science and Technology; 3. The North Portugal Regional Operational Program, under the Portugal 2020 Partnership agreement, through the European Regional Development Fund [grant number NORTE-01-0145-FEDER-000005 — LEPABE-2-ECO-INNOVATION, and NORTE-01-0145-FEDER-000029]; 4. and the Portuguese Foundation for Science and Technology, and Biomode 2, S.A. [grant number SFRH/BDE/51909/2012].