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Nucleic Acids Research, 1995, Vol. 23, No. 15 3003-3008
© 1995

MOLECULAR BIOLOGY

Inhibition of NF-{kappa}B specific transcriptional activation by PNA strand invasion

imothy A. Vickers, Michael C. Griffith, Kanda Ramasamy1, Lisa M. Risen and Susan M. Freier*

ISIS Pharmaceuticals 2292 Faraday Avenue, Carlsbad, CA 92008, USA 1ICN Pharmaceuticals ICN Plaza, 3300 Hyland Avenue, Costa Mesa, CA 92626, USA

*To Whom correspondence should be accepted

Received March 6, 1995. Accepted June 21, 1995.

Peptide nucleic acid (PNA) strand invasion offers an attractive alternative to DNA oligonucleotlde directed triplex formation as a potential tool for gene inhibition. Peptide nucleic acid has been shown to interact with duplex DNA in a process which involves strand Invasion of the duplex and binding of one of the DNA strands with two PNA oligomers. By blocking the interaction of a transcription factor with 5' regulatory sequences, PNA might specifically down-regulate gene activity. Here we demonstrate that PNA is capable of specifically blocking interaction of the transcription factor NF-{kappa}B with the IL2-R{alpha} NF{kappa}-B binding site In vitro. We further demonstrate that this interaction is sufficient to prevent transcriptional transactivation both In vitro and when transfected into cells in culture.


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