Prospects for the therapeutic use of antigene oligonucleotides

Cancer Invest. 1996;14(1):66-82. doi: 10.3109/07357909609018437.

Abstract

An outgrowth of classic nucleic acid interaction studies, oligonucleotide-directed triple helix formation is a unique method for creating highly specific chemical ligands that recognize and bind to particular sequences of duplex DNA. Under permissive conditions, these oligonucleotide-based compounds can approach or exceed the binding affinity and sequence specificity of natural DNA-binding proteins. Triple helix recognition has been found to be useful in certain cell-free applications including precise chromosome fragmentation. It has been proposed that such oligonucleotides could also form the basis for gene-targeted (antigene) drugs that might repress transcription from undesired genes in living cells. However, current strategies for oligonucleotide-directed triple helix formation suffer from important constraints involving requirements for stabilizing binding conditions, restrictions on permitted target sequences, and inefficient nuclear delivery of oligonucleotides. Implementation of oligonucleotide-directed triple helix formation as a viable approach to cancer therapy must therefore await clever solutions to a series of fascinating problems.

Publication types

  • Review

MeSH terms

  • Animals
  • DNA / drug effects
  • DNA / genetics
  • Gene Expression Regulation / drug effects
  • Humans
  • Nucleic Acid Conformation
  • Oligonucleotides, Antisense / pharmacology*
  • Thionucleotides / pharmacology*

Substances

  • Oligonucleotides, Antisense
  • Thionucleotides
  • DNA