Sequence-specific control of gene expression by antigene and clamp oligonucleotides

Ciba Found Symp. 1997;209:94-102; discussion 102-6. doi: 10.1002/9780470515396.ch8.

Abstract

Control of gene expression at the transcriptional level can be achieved with triplex-forming oligonucleotides provided that the target sequence is accessible within the chromatin structure of cell nuclei. Using oligonucleotide-psoralen conjugates as probes we have shown that the promoter region of the gene encoding the alpha subunit of the interleukin 2 receptor and the polypurine tract of integrated HIV provirus can form sequence-specific, triple-helical complexes in cell cultures. Oligonucleotide-intercalator conjugates can inhibit transcription initiation by competing with transcription factor binding. Oligonucleotide analogues containing N3'-->P5' phosporamidate linkages form stable triple helices that are able to arrest transcription at the elongation step. A triple helix can also be formed on a single-stranded target by clamp oligonucleotides. A clamp targeted to the polypurine tract of HIV RNA is able to block reverse transcription of the viral RNA.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA / drug effects
  • Gene Expression Regulation*
  • Humans
  • Nucleic Acid Conformation
  • Oligonucleotides, Antisense / pharmacology*
  • Protein Biosynthesis
  • Transcription, Genetic

Substances

  • Oligonucleotides, Antisense
  • DNA