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Gene delivery from a DNA controlled-release stent in porcine coronary arteries

Nature Biotechnology volume 18, pages 1181–1184 (2000)Cite this article

Abstract

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.

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Figure 1: DNA within stent coating.
Figure 2: DNA sustained release.
Figure 3: Cell transfection with GFP plasmid DNA into A10 cells using a DNA–PLGA coated stent wire.
Figure 4: Photomicrographs of arteries deployed in vivo with DNA–PLGA coated stents (A and D) or control PLGA-coated stents (B and E).
Figure 5: Representative PCR analyses of tissues for GFP distribution after left circumflex and left anterior descending coronary arterial deployment of DNA–PLGA coated stents in vivo.

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Acknowledgements

The authors thank Ms. Ginger Nicholson for her efforts in preparing the manuscript. We also thank Dr. Senator Hazelwood and Dr. Kenneth Ryan, Children's Hospital of Philadelphia, for their critical comments. We also thank Mark Bove and Angela Vicencio for technical assistance. We especially thank Dr. George Papandreou of the Cordis Corporation (Johnson & Johnson), for both making stents available, and providing supportive advice and encouragement. This work was supported in part by a research grant from Selective Genetics, Inc. Robert J. Levy is a recipient of an endowed chair from The Children's Hospital of Philadelphia. Crown stents were supplied by Cordis Corporation, Warren, NJ.

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Authors and Affiliations

  1. Division of Cardiovascular Diseases, University of Pennsylvania Medical Center, Philadelphia, PA

    Bruce D. Klugherz, Nicolas F. Meneveau & Robert L. Wilensky

  2. Children's Hospital of Philadelphia, Philadelphia , PA

    Peter L. Jones, Xiumin Cui, Weiliam Chen, Suzanne DeFelice, Jeanne Connolly & Robert J. Levy

Authors
  1. Bruce D. Klugherz
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  2. Peter L. Jones
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  3. Xiumin Cui
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  4. Weiliam Chen
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  5. Nicolas F. Meneveau
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  7. Jeanne Connolly
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  8. Robert L. Wilensky
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  9. Robert J. Levy
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Correspondence to Robert J. Levy.

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Klugherz, B., Jones, P., Cui, X. et al. Gene delivery from a DNA controlled-release stent in porcine coronary arteries. Nat Biotechnol 18, 1181–1184 (2000). https://doi.org/10.1038/81176

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