Nonconventional chemical inhibitors of microRNA: therapeutic scope

Chem Commun (Camb). 2015 Jan 18;51(5):820-31. doi: 10.1039/c4cc04514a. Epub 2014 Oct 20.


MicroRNAs (miRNAs) are a class of genomically encoded small RNA molecules (∼22nts in length), which regulate gene expression post transcriptionally. The term microRNA or miRNA was coined in 2001, and research in the past decade has shed light on their widespread occurrence, evolutionary conservation and tissue specific functions. It is estimated that they modulate the gene expression of approximately 60% of the mammalian genes by regulating the levels of target mRNAs to which they can bind on the basis of sequence complementarities. miRNAs are produced in a well coordinated series of steps from being transcribed in the nucleus to exerting their function in the cytoplasm. miRNAs are now implicated in diverse biological phenomena ranging from development to stress response which makes miRNAs one of the central regulatory molecules which modulate information flow along the central dogma of gene expression. More importantly, like any regulatory molecule, deregulation of miRNAs is causally associated with several diseases (mainly cancer) and is directly involved in a variety of pathophysiologies owing to their aberrant expression. Thus, modulation of miRNA levels is of prime therapeutic importance. Conventional methods of miRNA knockdown using chemically modified antisense-oligonucleotides have been explored extensively but face the challenges of modes of delivery, biostability and biodistribution. This calls for the development of more alternative and non-conventional methods to target miRNA. Small molecules targeting RNA chemical and structural space provide one such timely opportunity. In this article we first provide a brief overview of miRNA biogenesis and its disease associations. We then summarize the major developments in conventional oligonucleotide based approaches to miRNA knockdown and its status. We then focus on the more non-conventional methods like oligonucleotide enzymes and small molecules and provide an outlook on the future of such methods.

Publication types

  • Review

MeSH terms

  • Animals
  • Disease / etiology
  • Disease / genetics
  • Drug Discovery / methods*
  • Humans
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics
  • Small Molecule Libraries / pharmacology
  • Small Molecule Libraries / therapeutic use


  • MicroRNAs
  • Small Molecule Libraries