title: Efficient in vivo delivery of antisense oligonucleotide to choroid plexus.
abstract: The choroid plexus (CP) is present on the ventricular walls of the brain, produces cerebrospinal fluid (CSF), contains many blood vessels, and is a major functional component of the blood-CSF barrier. The CP is an important site in the pathophysiology of various neurological diseases, including Alzheimer's disease and meningeal amyloidosis. We performed gene silencing in the CP in vivo by using an antisense oligonucleotide (ASO). A short ASO of length 12 nucleotides was intravenously injected into rats. The ASO was not delivered to neurons or glia in the central nervous system, but was successfully delivered into the CP, and resulted in a significant reduction of endogenous target gene expression in epithelial cells within the CP. Although the mechanism of uptake of the ASO by the CP was not elucidated, the ASO bound to albumin in vivo, and the distribution of ASO delivery was similar to that of albumin delivery. These findings suggest that we inhibited target gene expression in the epithelial cells of the CP via albumin-ASO conjugates. This strategy should be useful for investigations of the function of CP, and for the development of new gene-silencing therapies for diseases with pathophysiology related to the CP.
authors.affiliation: Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Wenying
authors.initials: W
authors.lastname: Piao
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Nishina
authors.forename: Kie
authors.initials: K
authors.lastname: Yoshida-Tanaka
authors.forename: Hiroya
authors.initials: H
authors.lastname: Kuwahara
authors.forename: Tomoko
authors.initials: T
authors.lastname: Nishina
authors.forename: Mina
authors.initials: M
authors.lastname: Sakata
authors.forename: Hidehiro
authors.initials: H
authors.lastname: Mizusawa
authors.forename: Takanori
authors.initials: T
authors.lastname: Yokota
mesh_terms: D000418:Albumins / Q000378:metabolism; D000818:Animals; D002232:Carbocyanines; D018929:Cell Culture Techniques; D002460:Cell Line; D002831:Choroid Plexus / Q000378:metabolism*; D016503:Drug Delivery Systems; D004847:Epithelial Cells / Q000378:metabolism; D005240:Feasibility Studies; D005260:Female; D005456:Fluorescent Dyes; D020868:Gene Silencing / Q000187:drug effects; D018390:Gene Targeting / Q000379:methods; D007275:Injections, Intravenous; D051379:Mice; D008815:Mice, Inbred Strains; D018613:Microscopy, Confocal; D009841:Oligonucleotides / Q000008:administration & dosage / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000008:administration & dosage* / Q000235:genetics; D054735:Phosphorothioate Oligonucleotides / Q000008:administration & dosage / Q000235:genetics; D011485:Protein Binding; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013050:Spectrometry, Fluorescence; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: D000418:Albumins; D002232:Carbocyanines; D005456:Fluorescent Dyes; D009841:Oligonucleotides; D016376:Oligonucleotides, Antisense; D054735:Phosphorothioate Oligonucleotides; C089187:cyanine dye 3; C477371:locked nucleic acid; C000606291:Sod1 protein, mouse; C000606292:Sod1 protein, rat; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1