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the advent of the drug-eluting stent, the incidence of in-stent restenosis remains unacceptably high. Gene therapeutic strategies, including catheter-based gene delivery and gene-eluting stents, offer novel treatment methods to promote re-endothelialization, and inhibit inflammation, neointimal hyperplasia and late stent thrombosis. The translation of gene therapy into clinical application must be safe and requires an effective, site-specific delivery system as well as the ability to provide sustained transgene expression. The progress of magnetic nanotechnology and genetic engineering of human stem cells can provide such elements. In the present review, the authors discuss the evolution of antirestenosis therapy, underlying mechanisms of restenosis and the applications of gene therapy to prevent in-stent restenosis. Current gene delivery methods, including gene vectors and delivery strategies, are critically reviewed.