Gene activation by triplex-forming oligonucleotide coupled to the activating domain of protein VP16.
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.
Kuznetsova
S
S
Laboratory of Nucleic Acid Chemistry, Lomonosov Moscow State University, Leninskie gory, 119899, Moscow, Russia.
Ait-Si-Ali
S
S
Nagibneva
I
I
Troalen
F
F
Le Villain
J P
JP
Harel-Bellan
A
A
Svinarchuk
F
F
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D002460:Cell Line; D005786:Gene Expression Regulation; D017405:Herpes Simplex Virus Protein Vmw65 / Q000378:metabolism*; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000378:metabolism*; D015533:Transcriptional Activation
D017405:Herpes Simplex Virus Protein Vmw65; D009841:Oligonucleotides