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An Introduction to Molecular Medicine and Gene Therapy - part 6

Kết hợp gen chuyển và transmyocardial tia laser revascularization (TMR). Xem chèn màu sắc. Sơ đại diện của thiếu máu cục bộ mãn tính gây ra bởi vị trí của cuốn chặt lại Ameroid xung quanh động mạch vành dấu mu ở lợn. Trái tim thiếu máu cục bộ đã trải qua TN4R theo sau bằng cách tiêm của VEGF | GENE THERAPY FOR ANGIOGENESIS 191 FIGURE 8.3 Combined gene transfer and transmyocardial laser revascularization TMR . See color insert. Schematic representation of chronic ischemia induced by placement of Ameroid constrictor around the circumflex coronary artery in pigs. Ischemic hearts that underwent TN4R followed by injection of plasmid encoding VEGF demonstrated better normalization of myocardial function than either therapy alone. Porcine ameroid model of chronic ischemia Channel formation with CO2 laser Injection of plasmid adjacent to TMR site - VEGF vs. fig al factors or the genes encoding these factors have been administered to a small number of patients. These studies have involved either the use of angiogenic factors with peripheral vascular or coronary artery disease in patients who were not candidates for conventional revascularization therapies or the application of proan-giogenic factors as an adjunct to conventional revascularization. The modest doses of either protein factors or genetic material delivered in these studies were not associated with any acute toxicities. Concerns remain however regarding the safety of potential systemic exposure to molecules known to enhance the growth of possible occult neoplasms or that can enhance diabetic retinopathy and potentially even occlusive arterial disease itself. Despite early enthusiasm there is little experience with the administration of live viral vectors to a large number of patients. Thus it is uncertain whether potential biological hazards of reversion to replication-competent states or mutation and recombination will eventually become manifest. In addition it is also unclear whether the clinical success of conventional revascularization which has involved the resumption of lost bulk blood flow through larger conduits will be reproduced via biological strategies that primarily increase microscopic collateral networks. It must also be remembered that neovascularization is itself a naturally occurring