Targeting Positioning Within The Cardiovascular Gene Delivery System - Containing Genes Bracket The Experimental Study

PTCA (Percutaneous Transluminal Coronary Angioplasty ) has become one of the most important strategies to treat coronary artery diseases. However, restenosis has been observed in pathological and clinical studies, and poses a formidable problem (15-60%). The gene therapy for restenosis has progressed for the development of transgenic technique. The most challenging issues for successful application of gene therapy to human diseases concern: (1) the choice of the relevant therapeutic gene, (2) the choice of promoter and regulatory sequences driving expression of the transgene; and (3) the vector used for delivery of the transgene into cells (that is, for transduction of target cells). The difficulties in the development of an effective percutanous gene deliver system to the diseased site without distal spread have proven to be a major hurdle to the advancement of vascular gene therapy. In the past decades, balloon catheters have been used for vector delivery. However, catheter-based gene delivery systems fail to limit systemic biodistribution of vector to circulation and distal organs.Endovascular stents represent an ideal platform for localized vascular gene therapy for vascular diseases due to their permanent scaffolding structure. Because of long-term residue within the vessel, the gene tethered on the stent could release slowly and access the vascular cells directly. There are essentially two classes of gene therapy vectors: nonviral vectors and viral vectors. Viruses are efficient in transducing cells. However, the safety concerns regarding the use of virus in humans make nonviral delivery systems an attractive alternative. Nonviral vectors are particularly suitable with respect to simplicity of use, ease of large-scale production and lack of specific immune response. Recently, several novel nonviral vectors have been developed that approach viruses with respect to transfection efficiency. Among them, cationic lipid and chitosan have been extensively studied for gene vectors.To resolve the difficult problem of vascular gene therapy, we attached DAC system and chitosan-plasmid DNA nanoparticles on coronary stents to assesss the feasibility and effectivity of this novel gene delivery system.In chapter 1, the recent progress of the research topic was reviewed.