Pharmacology of Antisense Drugs

Annu Rev Pharmacol Toxicol. 2017 Jan 6;57:81-105. doi: 10.1146/annurev-pharmtox-010716-104846. Epub 2016 Oct 10.


Recent studies have led to a greater appreciation of the diverse roles RNAs play in maintaining normal cellular function and how they contribute to disease pathology, broadening the number of potential therapeutic targets. Antisense oligonucleotides are the most direct means to target RNA in a selective manner and have become an established platform technology for drug discovery. There are multiple molecular mechanisms by which antisense oligonucleotides can be used to modulate RNAs in cells, including promoting the degradation of the targeted RNA or modulating RNA function without degradation. Antisense drugs utilizing various antisense mechanisms are demonstrating therapeutic potential for the treatment of a broad variety of diseases. This review focuses on some of the advances that have taken place in translating antisense technology from the bench to the clinic.

Keywords: RNA; RNA interference; RNA splicing; RNase H; antisense oligonucleotides; eteplirsen; mipomersen; nusinersen; oligonucleotide; patisiran.

Publication types

  • Review

MeSH terms

  • Animals
  • Autoimmune Diseases / drug therapy
  • Autoimmune Diseases / metabolism
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / metabolism
  • Humans
  • Oligonucleotides, Antisense / metabolism
  • Oligonucleotides, Antisense / pharmacology*
  • Oligonucleotides, Antisense / therapeutic use*
  • RNA Interference / drug effects
  • RNA Interference / physiology
  • RNA Splicing / drug effects
  • RNA Splicing / physiology


  • Oligonucleotides, Antisense