title: Antigene-block strategy: effective regulation of gene expression by 2',4'-BNA-modified TFOs with an additional stem-loop structure.
abstract: Antigene strategy is promising technology to regulate gene expression. We have previously reported that 2'-O,4'-C-methylene bridged nucleic acid (2',4'-BNA) modification of triplex-forming oligonucleotides (TFOs) significantly enhanced the binding affinity towards the target dsDNA. In spite of its usefulness, the TFO-binding site may not completely overlay the protein-binding site because of the limitation of TFOs targeting sequences. To overcome this problem, we developed an antigene-based new methodology called "antigene-block" strategy. In this methodology, the TFOs bearing a bulky hairpin tail are used for efficient inhibition of protein-DNA interaction. The antigene-block TFOs having 2',4'-BNA modifications formed stable triplexes with the homopurine-homopyrimidine sequence which partially overlap the transcription factor NF-kappaB binding site. In addition, the antigene-block TFOs significantly reduced the expression level of the target-gene in living cells, while conventional 2',4'-BNA-modified or unmodified TFOs showed no effect on the target-gene expression.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita, Osaka 565-0871, Japan.
authors.forename: Naoto
authors.initials: N
authors.lastname: Tsuda
authors.forename: Ayumi
authors.initials: A
authors.lastname: Matsumoto
authors.forename: Aya
authors.initials: A
authors.lastname: Ito
authors.forename: Tomomi
authors.initials: T
authors.lastname: Uneda
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Tanabe
authors.forename: Satoshi
authors.initials: S
authors.lastname: Obika
authors.forename: Takeshi
authors.initials: T
authors.lastname: Imanishi
mesh_terms: D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D002522:Chlorocebus aethiops; D004247:DNA / Q000737:chemistry*; D005786:Gene Expression Regulation; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009690:Nucleic Acid Conformation; D009841:Oligonucleotides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D009841:Oligonucleotides; C051802:triplex DNA; D004247:DNA