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The ability to deliver therapeutic genes site specifically in vivo remains the major challenge for research in the field. The obligate need to target gene expression to the cells of interest in a selective, efficient and safe manner has become increasingly evident as a result of recent events in the clinical setting. The potential for gene transfer to treat cardiovascular disease is great, yet identified and unidentified barriers remain. Retroviral, adenoviral or liposome based vectors have been used and are in clinical trials already. The route of gene delivery is usually by intracardiac injection, retrograde and antegrad perfusion of the coronary arteries. We have recently described a new experimental catheter-based closed chest approach for myocardial gene delivery in rodents. Using arterial and venous balloon catheters to simultaneously induce aortic and right atrial occlusions for the intracoronary delivery of LacZ adenoviral vectors combined with transient cardiac arrest of 5-min to prolong the viral incubation time within the heart yielded an in-vivo transfection efficiency of about 43 %. Vascular permeabilization by SNAP or histamine did not further improve transfection efficiency, while a high intravascular pressure delivery approach proved to be rather inefficient (3-5 %). Ideally, one would like to target vascular endothelium and/or cardiomyocytes; however, the present efficiency is still rather low but can be improved by targeting peptides of high affinity to membrane proteins. Promising effects have been obtained with the transfer of genes for vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), tissue inhibitor of metalloproteinase (TIMP), hepatic growth factor (HGF) and NO-synthase. Several phase I and II clinical trials in general have shown the safety and therapeutic potential of gene-induced angiogenesis. However, future improvements of gene delivery techniques and vectors are still required before the full therapeutic potential of gene therapy for cardiac and vascular disorders can be realized.
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