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

被引:25
作者
Hino, T
Yokota, T [1 ]
Ito, S
Nishina, K
Kang, YS
Mori, S
Hori, S
Kanda, T
Terasaki, T
Mizusawa, H
机构
[1] Tokyo Med & Dent Univ, Grad Sch, Dept Neurol & Neurol Sci, Tokyo, Japan
[2] Tohoku Univ, Grad Sch Pharmaceut Sci, Dept Mol Biopharm & Genet, Sendai, Miyagi, Japan
[3] Sookmyung Womens Univ, Coll Pharm, Seoul, South Korea
关键词
small interfering RNA; blood-brain barrier; organic anion transporter 3; brain ischemia; brain inflammation; drug delivery system;
D O I
10.1016/j.bbrc.2005.11.173
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (c) 2005 Elsevier Inc. All rights reserved.
引用
收藏
页码:263 / 267
页数:5
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