Development of Human CBF1-Targeting Single-Stranded DNA Aptamers with Antiangiogenic Activity in Vitro

Mari Tezuka-Kagajo, Masashi Maekawa, Atsushi Ogawa, Yoshiko Hatta, Eiichi Ishii, Mariko Eguchi, Shigeki Higashiyama

研究成果: Article査読

4 被引用数 (Scopus)

抄録

C promoter binding factor 1 (CBF1) (alias RBPJ) is a critical transcription factor involved in Notch signaling. The activation of Notch signaling through CBF1 maintains the angiostatic state of endothelial cells suppressing angiogenesis, that is, the formation of new blood vessels. Vascular endothelial growth factor (VEGF) induces angiogenesis by promoting the proteasomal degradation of CBF1, in addition to endothelial cell proliferation. To date, angiogenic inhibitors targeting VEGF have been successfully used in clinics for cancer and age-related macular degeneration. Most antiangiogenic drugs, however, only target VEGF or VEGF receptors. In this study, to expand the repertoire of antiangiogenic therapeutics, we developed 15 single-stranded deoxyribonucleic acid (ssDNA) aptamers capable of binding to CBF1 with high affinity (Kd; 10-300 nM). To this end, systematic evolution of ligands by the exponential enrichment (SELEX) method was applied. One of the CBF1-binding ssDNA aptamers, Apt-3, inhibited angiogenesis through the activation of Notch signaling in vitro. We found that Apt-3 directly interacted with the LAG1 domain of CBF1. We suggest that the Apt-3 ssDNA aptamer may contribute to the development of a novel angiogenic inhibitor, which does not target VEGF.

本文言語English
ページ(範囲)365-378
ページ数14
ジャーナルNucleic Acid Therapeutics
30
6
DOI
出版ステータスPublished - 2020 12月
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子医療
  • 分子生物学
  • 遺伝学
  • 創薬

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