title: Vascular oligonucleotide transfer facilitated by a polymer-coated stent.
abstract: To evaluate the potential of clinically used phosphorylcholine (PC)-coated stents for their ability to load and release small decoy oligonucleotides (ODNs). Stents were loaded with 41 +/- 6 microg ODNs. Ex vivo deployment of ODN-loaded stents in explanted rabbit aortas showed significant vascular ODN transfer, with 18 +/- 12% of intimal or medial cell nuclei containing ODNs. In proof-of-principle in vivo experiments (using the double-injury rabbit model) there was no difference in fluorescent signal intensity between animals receiving ODNloaded stents or controls. However, a significant increase in signal intensity was detected in the kidneys of animals receiving ODN-loaded stents. PC-coated stents can be loaded with ODNs. Despite successful ex vivo ODN deposition and nuclear uptake in the vessel wall, in vivo vascular ODN transfer was not achieved. Rapid intravascular release of ODN before implantation and potential vascular barriers for gene transfer are most likely responsible for the currently unsatisfactory in vivo release kinetics.
authors.affiliation: Department of Gene Therapy, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, SW3 6LR, UK.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Radke
authors.forename: Uta
authors.initials: U
authors.lastname: Griesenbach
authors.forename: Antti
authors.initials: A
authors.lastname: Kivela
authors.forename: Terry
authors.initials: T
authors.lastname: Vick
authors.forename: Diane
authors.initials: D
authors.lastname: Judd
authors.forename: Felix
authors.initials: F
authors.lastname: Munkonge
authors.forename: Sean
authors.initials: S
authors.lastname: Willis
authors.forename: Duncan M
authors.initials: DM
authors.lastname: Geddes
authors.forename: Seppo
authors.initials: S
authors.lastname: Yla-Herttuala
authors.forename: Eric W F W
authors.initials: EW
authors.lastname: Alton
mesh_terms: D000818:Animals; D001011:Aorta / Q000601:surgery; D001808:Blood Vessels / Q000502:physiology*; D020099:Coated Materials, Biocompatible; D016650:Fluorescein-5-isothiocyanate / Q000032:analysis; D018014:Gene Transfer Techniques; D007668:Kidney / Q000502:physiology; D008297:Male; D016328:NF-kappa B / Q000235:genetics; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000235:genetics / Q000493:pharmacokinetics; D010767:Phosphorylcholine; D011817:Rabbits; D015607:Stents; D014162:Transfection / Q000379:methods
chemical_list: D020099:Coated Materials, Biocompatible; D016328:NF-kappa B; D009841:Oligonucleotides; D010767:Phosphorylcholine; D016650:Fluorescein-5-isothiocyanate