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Title:
Intravenous siRNA of Brain Cancer with Receptor Targeting and AvidināBiotin Technology | Pharmaceutical Research
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Purpose 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 bloodābrain barrier in vivo. Methods siRNA was delivered to brain in vivo with the combined use of a receptor-specific monoclonal antibody delivery system, and avidinābiotin 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. Results 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 biotināstreptavidin linker. The intravenous administration of the siRNA caused a 69ā81% decrease in luciferase gene expression in the intracranial brain cancer in vivo. Conclusions 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 avidinābiotin technology.
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Keywords {š}
article, google, scholar, pubmed, cas, brain, pardridge, gene, sirna, delivery, vivo, zhang, receptor, rna, intravenous, targeting, boado, bloodbrain, barrier, antibody, cancer, research, interfering, monoclonal, small, privacy, cookies, content, technology, cells, access, rnas, human, res, ther, usa, publish, search, avidinbiotin, administration, methods, transferrin, expression, silencing, interference, physiol, analysis, data, information, log,
Topics {āļø}
month download article/chapter anti-transferrin receptor antibody induce sequence-specific silencing primate bloodābrain barrier human insulin receptor brain drug-targeting technology pubmedĀ google scholar transferrin receptor antibody bloodābrain barrier sirna-induced caveolin-1 knockdown related subjects avidinābiotin technology small interfering rna nucleic acid analogue monoclonal antibody short interfering rna rna interference transferrin receptor serves blood flow metab privacy choices/manage cookies full article pdf luciferase gene expression rna affinity vector-mediated delivery small interfering rnas human brain capillaries effective brain targeting cerebral microvascular permeability short hairpin rnas google scholar imaging brain amyloid single intravenous injection receptor targeting biotināstreptavidin linker european economic area intra-cranial tumors experimental neuro-oncology central nervous systemnature intravenous rnai conditions privacy policy intravenous administration requires article xia gene expression abeta peptide radiopharmaceutical somatic mammalian cells cultured mammalian cells biotin delivery gene silencing intracranial brain cancer improve sirna specificity
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headline:Intravenous siRNA of Brain Cancer with Receptor Targeting and AvidināBiotin Technology
description: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 bloodābrain barrier in vivo. siRNA was delivered to brain in vivo with the combined use of a receptor-specific monoclonal antibody delivery system, and avidinābiotin 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 biotināstreptavidin linker. The intravenous administration of the siRNA caused a 69ā81% 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 avidinābiotin technology.
datePublished:2007-10-11T00:00:00Z
dateModified:2007-10-11T00:00:00Z
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biotin
bloodābrain barrier
monoclonal antibody
RNA interference
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Pharmacy
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general
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Biomedical Engineering and Bioengineering
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headline:Intravenous siRNA of Brain Cancer with Receptor Targeting and AvidināBiotin Technology
description: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 bloodābrain barrier in vivo. siRNA was delivered to brain in vivo with the combined use of a receptor-specific monoclonal antibody delivery system, and avidinābiotin 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 biotināstreptavidin linker. The intravenous administration of the siRNA caused a 69ā81% 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 avidinābiotin technology.
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bloodābrain barrier
monoclonal antibody
RNA interference
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Pharmacy
Biochemistry
general
Medical Law
Biomedical Engineering and Bioengineering
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