Antibody-mediated targeting of siRNA via the human insulin receptor using avidin-biotin technology.
Antibody-mediated targeting of siRNA via the human insulin receptor using avidin-biotin technology.
复制标题
使用抗生物素蛋白-生物素技术通过人胰岛素受体进行抗体介导的 siRNA 靶向。
DOI：
10.1021/mp800194y
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发表时间：
2009
影响因子：
4.9
通讯作者：
Pardridge,WilliamM
中科院分区：
文献类型：
--
作者：
Xia,Chun-Fang;Boado,RubenJ;Pardridge,WilliamM
Delivery of short interfering RNA (siRNA) to cells in culture, and in vivo, is possible with combined use of a receptor-specific monoclonal antibody (mAb) and avidin−biotin technology. In the present studies, the luciferase gene is transiently expressed in human 293 epithelial cells. The siRNA delivery system is composed of the siRNA, monobiotinylated on the 3′-terminus of the sense strand, and a conjugate of streptavidin (SA) and a mAb to the human insulin receptor (HIR). Exposure of cells to 3′-biotinyl-siRNA bound to the HIRMAb/SA conjugate, but not to unconjugated SA, avidin, or the HIRMAb, causes a >90% reduction in luciferase gene expression. The receptor-targeted siRNA effect is maximal at 48 h after delivery of the siRNA to the cells, and the effect is lost by 7 days after a single application of the targeted siRNA in culture. The KI of the receptor-targeted siRNA inhibition of gene expresssion is 30.5 ± 11.7 nM, and significant inhibition is observed with siRNA concentrations as low as 3 nM. In conclusion, the combination of a receptor-specific targeting ligand, such as the HIRMAb, and avidin−biotin technology allows for high affinity capture of the monobiotinylated siRNA by the targeting mAb. The siRNA is effectively delivered to the cytosol of cells, and knockdown of gene expression with the HIRMAb/SA delivery system is comparable to RNA interference effects obtained with cationic polyplexes. Whereas the use of cationic polyplexes in vivo is problematic, the bond between the targeting mAb and the siRNA is stable with avidin−biotin technology, and RNAi effects at distant sites such as brain are observed in vivo following an intravenous administration of the targeted siRNA.
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影响因子：
3.7
作者：
Coloma, MJ;Lee, HJ;Pardridge, WM
通讯作者：
Pardridge, WM
表皮生长因子放射性药物：111通过生物素-聚乙烯接头螯合、缀合至血脑屏障递送载体、药代动力学和实验性脑肿瘤的体内成像。
影响因子：
4.7
作者：
A. Kurihara;Y. Deguchi;W. Pardridge
通讯作者：
W. Pardridge
使用 Aβ 肽放射性药物对转基因小鼠体内阿尔茨海默病的脑淀粉样蛋白进行成像
影响因子：
6.3
作者：
H. Lee;Yun Zhang;Chunni Zhu;K. Duff;W. Pardridge
通讯作者：
W. Pardridge
DOI：
10.1016/s0169-328x(98)00134-x
发表时间：
1998-08-15
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Boado, RJ;Pardridge, WM
通讯作者：
Pardridge, WM
DOI：
--
发表时间：
2003
期刊：
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
影响因子：
--
作者：
B. Pettus;J. Bielawski;A. Porcelli;Davis L. Reames;Korey R. Johnson;J. Morrow;C. Chalfant;L. Obeid;Y. Hannun
通讯作者：
B. Pettus;J. Bielawski;A. Porcelli;Davis L. Reames;Korey R. Johnson;J. Morrow;C. Chalfant;L. Obeid;Y. Hannun