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Vascular oligonucleotide transfer facilitated by a polymer-coated stent
Peter W Radke1, Uta Griesenbach, Antti Kivela
1Department of Gene Therapy, National Heart and Lung Institute, Faculty of Medicine, Imperial College London, SW3 6LR, UK.
Human Gene Therapy
|June 18, 2005
Summary
Phosphorylcholine (PC)-coated stents can load oligonucleotides (ODNs). While ex vivo tests showed ODN transfer to vessel cells, in vivo studies did not achieve effective vascular ODN delivery, indicating challenges with current release kinetics.
Area of Science:
- Biomaterials Science
- Vascular Biology
- Gene Delivery
Background:
- Phosphorylcholine (PC)-coated stents are clinically used devices.
- Oligonucleotides (ODNs) are investigated for therapeutic gene modulation.
- Effective delivery of ODNs via stents remains a challenge.
Purpose of the Study:
- To assess the capacity of PC-coated stents to load and release small decoy ODNs.
- To evaluate the in vivo and ex vivo performance of ODN-loaded PC-coated stents for vascular gene transfer.
Main Methods:
- PC-coated stents were loaded with ODNs (41 ± 6 μg).
- Ex vivo studies involved deploying ODN-loaded stents in rabbit aortas.
- In vivo studies utilized a double-injury rabbit model to assess ODN delivery.
Main Results:
- Successful loading of ODNs onto PC-coated stents was achieved.
- Ex vivo deployment demonstrated significant ODN transfer (18 ± 12% cell nuclei uptake).
- In vivo studies showed no significant vascular signal but increased signal in kidneys; no difference vs. controls.
Conclusions:
- PC-coated stents can be loaded with ODNs, with successful ex vivo deposition and cellular uptake.
- Current in vivo vascular ODN transfer via these stents is not achieved.
- Rapid intravascular ODN release and potential vascular barriers limit in vivo gene transfer efficacy.