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Ciba Found Symp. 1997;209:94-102; discussion 102-6.

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

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1
Laboratoire de Biophysique, INSERM U 201, CNRS URA 481, Paris, France.

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.

PMID:
9383571
[Indexed for MEDLINE]
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