Intravenous siRNA of Brain Cancer with Receptor Targeting and Avidin–Biotin Technology
- Chun-Fang XiaAffiliated withDepartment of Medicine, UCLA
- , Yufeng ZhangAffiliated withArmaGen Technologies, Inc.
- , Yun ZhangAffiliated withDepartment of Medicine, UCLAArmaGen Technologies, Inc.
- , Ruben J. BoadoAffiliated withDepartment of Medicine, UCLAArmaGen Technologies, Inc.
- , William M. PardridgeAffiliated withDepartment of Medicine, UCLA Email author
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The effective delivery of short interfering RNA (siRNA) to brain following intravenous administration requires the development of a delivery system for transport of the siRNA across the brain capillary endothelial wall, which forms the blood–brain barrier in vivo.
siRNA was delivered to brain in vivo with the combined use of a receptor-specific monoclonal antibody delivery system, and avidin–biotin technology. The siRNA was mono-biotinylated on either terminus of the sense strand, in parallel with the production of a conjugate of the targeting MAb and streptavidin.
Rat glial cells (C6 or RG-2) were permanently transfected with the luciferase gene, and implanted in the brain of adult rats. Following the formation of intra-cranial tumors, the rats were treated with a single intravenous injection of 270 μg/kg of biotinylated siRNA attached to a transferrin receptor antibody via a biotin–streptavidin linker. The intravenous administration of the siRNA caused a 69–81% decrease in luciferase gene expression in the intracranial brain cancer in vivo.
Brain delivery of siRNA following intravenous administration is possible with siRNAs that are targeted to brain with the combined use of receptor specific antibody delivery systems and avidin–biotin technology.
Key wordsavidin biotin blood–brain barrier monoclonal antibody RNA interference
- Intravenous siRNA of Brain Cancer with Receptor Targeting and Avidin–Biotin Technology
Volume 24, Issue 12 , pp 2309-2316
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- Springer US
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- blood–brain barrier
- monoclonal antibody
- RNA interference
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