Gene delivery from a DNA controlled-release stent in porcine coronary
arteries
Bruce D. Klugherz1, Peter L. Jones2, Xiumin Cui2, Weiliam Chen2, Nicolas F. Meneveau1, Suzanne DeFelice2, Jeanne Connolly2, Robert L. Wilensky1
& Robert J. Levy2
1
Division of Cardiovascular Diseases, University of
Pennsylvania Medical Center, Philadelphia, PA.
2
Children's Hospital of Philadelphia, Philadelphia
, PA.
Correspondence should be addressed to Robert J. Levy levyr@email.chop.eduplasmidtransfectiondrug deliverypolymerangioplasty
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.