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

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)365-378
Number of pages14
JournalNucleic Acid Therapeutics
Volume30
Issue number6
DOIs
Publication statusPublished - 2020 Dec
Externally publishedYes

Keywords

  • CBF1
  • DNA aptamer
  • Notch
  • angiogenesis

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Drug Discovery

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