Gene transfer stents

Gene therapy offers new possibilities for the treatment of cardiovascular diseases. This area of research has focused mainly on the treatment of postangioplasty restenosis, in-stent restenosis, and vein graft thickening. First clinical trials have shown that vascular gene transfer to humans is generally safe and well tolerated. Even... 

Van Belle E, Tio FO, Chen D, et al. Fhssivation of metallic stents after arterial gene transfer of phVEGF 165 inhibits thrombus formation and intimal thickening. J Am Coll Cardiol 1997 6 1371-1379. 

Walter DH, Cejna M, Diaz-Sandoval L, et al. Local gene transfer of phVEGF-2 plasmid by gene-eluting stents an alternative strategy for inhibition of restenosis. Circulation 2004 I 10( I ) 36—45. 

Klugherz BD, Chen w, Jones PL, et al. Successful gene transfer to the arterial wall using a DNA-eluting polymer-coated intracoronary stent in swine [abstr], Eur Heart J 1999 20 367. 

Yuan J, Gao R, Shi R, et al. Intravascular local gene transfer mediated by protein-coated metallic stent, Chin Med J (Engl) 2001 I 14(10) 1043-1045. 

Panetta CJ, Miyauchi K, Berry D, et al, A tissue-engineered stent for cell-based vascular gene transfer, Hum Gene Ther 2002 13(3)433-441. 

The kuopio angiogenesis trial (KAT), a phase II clinical trial involving 103 patients, used adenovirus gene transfer for VEGF mainly in stented patients, At six months, no detectable difference was seen in restenosis rates compared with controls, but there was a significant improvement in myocardial perfusion (47). 

Hedman M, Hartikainen J, Syvanne M, et al. Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia. Circulation 2003 107 2677-2683. 

Van Belle E, Maillard L, Rivard A, et al. Effects of poloxamer 407 on transfection time and percutaneous adenovirus-mediated gene transfer in native and stented vessels. Hum Gene Ther 1998 9 1013-1024. 

Yamauchi, F., et al. Layer-by-layer assembly of cationic lipid and plasmid DNA onto gold surface for stent-assisted gene transfer. Biomaterials 27(18), 3497-3504 (2006)... 

Nakayama Y., Kim J.-Y., Ueno H., Matsuda T. Development of high-performance stent Gelatinous photogel-coated stent that permits drug delivery and gene transfer. J. Biomed. Mater. Res. 2001 57 559-566... 

Hedman, M., Hartikainen, J., Syvanne, M., Stjernvall, J., Hedman, A., Kivela, A., Vanninen, E., Mussalo, H., Kauppila, E., Simula, S., Narvanen, O., Rantala, A., Peuhkurinen, K., Nieminen, M. S., Laakso, M., and Yla-Herttuala, S. 2003. Safety and feasibility of catheter-based local intracoronary vascular endothelial growth factor gene transfer in the prevention of postangioplasty and in-stent restenosis and in the treatment of chronic myocardial ischemia—Phase 11 results of the Kuopio Angiogenesis Trial (Kat). Circulation, 107,2677-2683. 

Radke PW, Griesenbach U, Kivela A, et al, Vascular oligonucleotide transfer facilitated by a polymer-coated stent. Hum Gene Ther 2005 I 6(6) 734-740. 

Several attempts in the past have been made to achieve local gene delivery via coated balloon catheters or infusion catheters using both naked plasmid DNA and adenoviral vectors for the transfer of VEGF-1 or -2 (69,70). Walter et al. (69) demonstrated that local VEGF-2 plasmid gene delivery of a therapeutic gene via coated stents appears feasible, safe, and effective. 

A narrowing of the blood vessels (restenosis) often occurs after coronary blood vessel dilatation by stent implantation. This is probably caused by the proliferation of smooth muscle cells following injuring of the blood vessel endothelium by the stent. Here, the role of adenoviral or plasmid DNA-mediated transfer of the gene encoding inducible nitroxid synthase (iNOS) is thought to result in reduced cell proliferation. 

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