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Keywords:

  • antisense oligonucleotide design;
  • cell-penetrating peptide;
  • dendrimer;
  • gapmer antisense oligonucleotide;
  • liposome;
  • locked nucleic acid;
  • peptide nucleic acid;
  • phosphoroamidate morpholino oligomer;
  • phosphorothioate;
  • RNase H

SUMMARY

  • 1
    An antisense oligonucleotide (ASO) is a short strand of deoxyribonucleotide analogue that hybridizes with the complementary mRNA in a sequence-specific manner via Watson–Crick base pairing. Formation of the ASO–mRNA heteroduplex either triggers RNase H activity, leading to mRNA degradation, induces translational arrest by steric hindrance of ribosomal activity, interferes with mRNA maturation by inhibiting splicing or destabilizes pre-mRNA in the nucleus, resulting in downregulation of target protein expression.
  • 2
    The ASO is not only a useful experimental tool in protein target identification and validation, but also a highly selective therapeutic strategy for diseases with dysregulated protein expression.
  • 3
    In the present review, we discuss various theoretical approaches to rational design of ASO, chemical modifications of ASO, ASO delivery systems and ASO-related toxicology. Finally, we survey ASO drugs in various current clinical studies.