In vivo delivery of small interfering RNA targeting brain capillary endothelial cells

Taro Hino, Takanori Yokota, Shingo Ito, Kazutaka Nishina, Young Sook Kang, Shinobu Mori, Satoko Hori, Takashi Kanda, Tetsuya Terasaki, Hidehiro Mizusawa

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Brain capillary endothelial cells (BCECs) play an important role in blood-brain barrier (BBB) functions and pathophysiologic mechanisms in brain ischemia and inflammation. We try to suppress gene expression in BCECs by intravenous application of small interfering RNA (siRNA). After injection of large dose siRNA with hydrodynamic technique to mouse, suppression of endogenous protein and the BBB function of BCECs was investigated. The brain-to-blood transport function of organic anion transporter 3 (OAT3) that expressed in BCECs was evaluated by Brain Efflux Index method in mouse. The siRNA could be delivered to BCECs and efficiently inhibited endogenously expressed protein of BCECs. The suppression effect of siRNA to OAT3 is enough to reduce the brain-to-blood transport of OAT3 substrate, benzylpenicillin at BBB. The in vivo siRNA-silencing method with hydrodynamic technique may be useful for the study of BBB function and gene therapy targeting BCECs.

Original languageEnglish
Pages (from-to)263-267
Number of pages5
JournalBiochemical and Biophysical Research Communications
Volume340
Issue number1
DOIs
Publication statusPublished - 2006 Feb 3
Externally publishedYes

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Keywords

  • Blood-brain barrier
  • Brain inflammation
  • Brain ischemia
  • Drug delivery system
  • Organic anion transporter 3
  • Small interfering RNA

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Hino, T., Yokota, T., Ito, S., Nishina, K., Kang, Y. S., Mori, S., Hori, S., Kanda, T., Terasaki, T., & Mizusawa, H. (2006). In vivo delivery of small interfering RNA targeting brain capillary endothelial cells. Biochemical and Biophysical Research Communications, 340(1), 263-267. https://doi.org/10.1016/j.bbrc.2005.11.173