Gene delivery from a DNA controlled-release stent in porcine coronary arteries.
Expandable intra-arterial stents are widely used for treating coronary disease. We hypothesized that local gene delivery could be achieved with the controlled release of DNA from a polymer coating on an expandable stent. Our paper reports the first successful transfection in vivo using a DNA controlled-release stent. Green fluorescent protein (GFP) plasmid DNA within emulsion-coated stents was efficiently expressed in cell cultures (7.9% +/- 0.7% vs. 0.6% +/- 0.2% control, p < 0.001) of rat aortic smooth muscle cells. In a series of pig stent-angioplasty studies, GFP expression was observed in all coronary arteries (normal, nondiseased) in the DNA-treated group, but not in control arteries. GFP plasmid DNA in the arterial wall was confirmed by PCR, and GFP presence in the pig coronaries was confirmed by immunohistochemistry. Thus, DNA-eluting stents are capable of arterial transfection, and could be useful as delivery systems for candidate vectors for gene therapy of cardiovascular diseases.
Klugherz
B D
BD
Division of Cardiovascular Diseases, University of Pennsylvania Medical Center, Philadelphia, PA, USA.
Jones
P L
PL
Cui
X
X
Chen
W
W
Meneveau
N F
NF
DeFelice
S
S
Connolly
J
J
Wilensky
R L
RL
Levy
R J
RJ
D000818:Animals; D052160:Benzothiazoles; D002318:Cardiovascular Diseases / Q000628:therapy; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000473:pathology*; D004247:DNA / Q000493:pharmacokinetics; D004587:Electrophoresis, Agar Gel; D005456:Fluorescent Dyes; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D007700:Kinetics; D008164:Luminescent Proteins / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000166:cytology / Q000378:metabolism; D010957:Plasmids / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011804:Quinolines; D051381:Rats; D015607:Stents; D013552:Swine; D013844:Thiazoles; D013997:Time Factors; D014162:Transfection
D052160:Benzothiazoles; D005456:Fluorescent Dyes; D008164:Luminescent Proteins; D011804:Quinolines; D013844:Thiazoles; C051000:thiazole orange; D049452:Green Fluorescent Proteins; D004247:DNA