Inhibition of NF-kappa B specific transcriptional activation by PNA strand invasion.
Peptide nucleic acid (PNA) strand invasion offers an attractive alternative to DNA oligonucleotide 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.
Vickers
T A
TA
ISIS Pharmaceuticals, Carlsbad, CA 92008, USA.
Griffith
M C
MC
Ramasamy
K
K
Risen
L M
LM
Freier
S M
SM
D001483:Base Sequence; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism*; D004274:DNA, Recombinant; D015536:Down-Regulation; D017930:Genes, Reporter / Q000235:genetics; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D009690:Nucleic Acid Conformation; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015375:Receptors, Interleukin-2 / Q000235:genetics; D015533:Transcriptional Activation; D014162:Transfection
D004274:DNA, Recombinant; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D010455:Peptides; D015375:Receptors, Interleukin-2; C051802:triplex DNA; D004247:DNA