Vascular oligonucleotide transfer facilitated by a polymer-coated stent.
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.
Radke
Peter W
PW
Department of Gene Therapy, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, SW3 6LR, UK.
Griesenbach
Uta
U
Kivela
Antti
A
Vick
Terry
T
Judd
Diane
D
Munkonge
Felix
F
Willis
Sean
S
Geddes
Duncan M
DM
Yla-Herttuala
Seppo
S
Alton
Eric W F W
EW
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
D020099:Coated Materials, Biocompatible; D016328:NF-kappa B; D009841:Oligonucleotides; D010767:Phosphorylcholine; D016650:Fluorescein-5-isothiocyanate