Myocardial gene transfer by selective pressure-regulated retroinfusion of coronary veins
2000; Springer Nature; Volume: 7; Issue: 3 Linguagem: Inglês
10.1038/sj.gt.3301079
ISSN1476-5462
AutoresPeter Boekstegers, Georges von Degenfeld, Wolfgang Giehrl, D. Heinrich, Roger Hullin, Christian Kupatt, Gerhard Steinbeck, Gustavo Baretton, Guido Middeler, Hugo A. Katus, Wolfgang-M. Franz,
Tópico(s)Virus-based gene therapy research
ResumoCatheter-based percutaneous transluminal gene delivery (PTGD) into the coronary artery still falls behind the expectations of an efficient myocardial gene delivery system. In this study gene delivery was applied by selective pressure-regulated retroinfusion through the coronary veins to prolong adhesion of replication defective adenovirus within the targeted myocardium. Adenoviral vectors consisted either of luciferase (Ad.rsv-Luc) or beta-galactosidase (Ad.rsv-betaGal) reporter gene under control of an unspecific promotor derived from the Rous sarcoma virus (RSV). In this pig model, selective retrograde gene delivery into the anterior cardiac vein during a brief period of ischemia substantially increased reporter gene expression in the targeted myocardium (LAD region) compared with antegrade delivery as a control. Repeated retrograde delivery during two periods of brief ischemia resulted in a more homogeneous transmural expression predominantly observed in cardiomyocytes (X-gal-staining). In the nontargeted myocardium (CX region) there was no evidence for adenoviral transfection. From our data we infer that selective pressure-regulated retroinfusion is a promising approach for efficient percutaneous transluminal gene delivery to the myocardium. Gene Therapy (2000) 7, 232-240.
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