Antigene-block strategy: effective regulation of gene expression by 2',4'-BNA-modified TFOs with an additional stem-loop structure.

Naoto Tsuda, Ayumi Matsumoto, Aya Ito, Tomomi Uneda, Atsuhiro Tanabe, Satoshi Obika, Takeshi Imanishi

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

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.

Original languageEnglish
Pages (from-to)335-336
Number of pages2
JournalNucleic acids symposium series (2004)
Issue number49
DOIs
Publication statusPublished - 2005

ASJC Scopus subject areas

  • Medicine(all)

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