In vivo delivery of small interfering RNA targeting brain capillary endothelial cells |
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Authors: | Hino Taro Yokota Takanori Ito Shingo Nishina Kazutaka Kang Young-Sook Mori Shinobu Hori Satoko Kanda Takashi Terasaki Tetsuya Mizusawa Hidehiro |
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Affiliation: | Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan. |
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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. |
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Keywords: | Small interfering RNA Blood-brain barrier Organic anion transporter 3 Brain ischemia Brain inflammation Drug delivery system |
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