Prospects for the therapeutic use of antigene oligonucleotides.
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.
Maher
L J
LJ
Department of Biochemistry and Molecular Biology, Mayo Foundation, Rochester, Minnesota 55905, USA.
D000818:Animals; D004247:DNA / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D009690:Nucleic Acid Conformation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology*
D016376:Oligonucleotides, Antisense; D013873:Thionucleotides; D004247:DNA