Nucleic Acids Research, Vol 27, Issue 20 3995-4000, Copyright © 1999 by Oxford University Press
S Kuznetsova, S Ait-Si-Ali, I Nagibneva, F Troalen, JP Le Villain, A Harel- Bellan and F Svinarchuk
Triplex-forming oligonucleotides (TFOs) are generally designed to inhibit
transcription or DNA replication but can be used for more diverse purposes.
Here we have designed a chimera peptide-TFO able to activate transcription
from a target gene. The designed hybrid molecule contains a triplex-forming
sequence, linked through a phosphoroamidate bond to several minimal
transcriptional activation domains derived from Herpes simplex virus
protein 16 (VP16). We show here that this TFO- peptide chimera (TFO-P) can
specifically recognise its DNA target at physiological salt and pH
conditions. Bound to the double-stranded target DNA in a promoter region,
the TFO-P is able to activate gene expression. Our results suggest that
this type of molecule may prove useful in the design of new tools for
artificial modulation of gene expression.
ARTICLES
Gene activation by triplex-forming oligonucleotide coupled to the activating domain of protein VP16
Laboratory of Nucleic Acid Chemistry, Lomonosov Moscow State University, Leninskie gory, 119899, Moscow, Russia.
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