Sequence-specific control of gene expression by antigene and clamp oligonucleotides.
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.
Hélène
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Laboratoire de Biophysique, INSERM U 201, CNRS URA 481, Paris, France.
Giovannangeli
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Guieysse-Peugeot
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Praseuth
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D
D000818:Animals; D004247:DNA / Q000187:drug effects; D005786:Gene Expression Regulation; D006801:Humans; D009690:Nucleic Acid Conformation; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D014176:Protein Biosynthesis; D014158:Transcription, Genetic
D016376:Oligonucleotides, Antisense; D004247:DNA