title: Intravenous siRNA of brain cancer with receptor targeting and avidin-biotin technology.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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 microg/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.
  
  
  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 avidin-biotin technology.
authors.affiliation: Department of Medicine, UCLA, Warren Hall 13-164, 900 Veteran Ave., Los Angeles, California, USA.
authors.forename: Chun-Fang
authors.initials: CF
authors.lastname: Xia
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhang
authors.forename: Ruben J
authors.initials: RJ
authors.lastname: Boado
authors.forename: William M
authors.initials: WM
authors.lastname: Pardridge
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism*; D001710:Biotin / Q000378:metabolism*; D019921:Biotinylation; D001812:Blood-Brain Barrier / Q000378:metabolism; D001932:Brain Neoplasms / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy*; D045744:Cell Line, Tumor; D018014:Gene Transfer Techniques; D017930:Genes, Reporter; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008297:Male; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D011972:Receptor, Insulin / Q000276:immunology; D011990:Receptors, Transferrin / Q000276:immunology*; D019809:Streptavidin / Q000378:metabolism*; D013997:Time Factors; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D034741:RNA, Small Interfering; D011990:Receptors, Transferrin; D001710:Biotin; D019809:Streptavidin; D008156:Luciferases; D011972:Receptor, Insulin