Morpholino antisense oligomers: the case for an RNase H-independent structural type

Biochim Biophys Acta. 1999 Dec 10;1489(1):141-58. doi: 10.1016/s0167-4781(99)00150-5.


RNase H-competent phosphorothioates (S-DNAs) have dominated the antisense field in large part because they offer reasonable resistance to nucleases, they afford good efficacy in cell-free test systems, they can be targeted against sites throughout the RNA transcript of a gene, and they are widely available from commercial sources at modest prices. However, these merits are counterbalanced by significant limitations, including: degradation by nucleases, poor in-cell targeting predictability, low sequence specificity, and a variety of non-antisense activities. In cell-free and cultured-cell systems where one wishes to block the translation of a messenger RNA coding for a normal protein, RNase H-independent morpholino antisense oligos provide complete resistance to nucleases, generally good targeting predictability, generally high in-cell efficacy, excellent sequence specificity, and very preliminary results suggest they may exhibit little non-antisense activity.

Publication types

  • Review

MeSH terms

  • Alternative Splicing / drug effects
  • Cell-Free System / enzymology
  • Drug Carriers / chemistry
  • Drug Design
  • Gene Expression / drug effects
  • Gene Targeting / methods
  • HeLa Cells
  • Humans
  • Morpholines / chemistry*
  • Nucleic Acid Hybridization / genetics
  • Oligonucleotides, Antisense / chemistry*
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / metabolism
  • Oligonucleotides, Antisense / pharmacology
  • Protein Biosynthesis / drug effects
  • RNA Processing, Post-Transcriptional / drug effects
  • Ribonuclease H / metabolism*
  • Substrate Specificity
  • Thionucleotides / chemistry
  • Thionucleotides / genetics
  • Thionucleotides / pharmacology


  • Drug Carriers
  • Morpholines
  • Oligonucleotides, Antisense
  • Thionucleotides
  • Ribonuclease H