Nonsurgical direct delivery of plasmid DNA into rat heart:: Time course, dose response, and the influence of different promoters on gene expression
Nonsurgical direct delivery of plasmid DNA into rat heart:: Time course, dose response, and the influence of different promoters on gene expression
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DOI：
10.1097/00005344-200202000-00008
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发表时间：
2002-02-01
影响因子：
3
通讯作者：
Islam, KB
中科院分区：
文献类型：
--
作者：
Sarkar, N;Blomberg, P;Islam, KB
将编码治疗性蛋白的基因转移到心肌中显示出治疗冠状动脉疾病的巨大潜力。为了定量阐明心脏基因转移后质粒DNA的行为，采用一种新的非手术直接递送方法，研究了大鼠心脏的时间动力学、剂量-反应关系、全身扩散到肝脏以及不同启动子对质粒DNA基因表达的影响。在超声心动图引导下，将编码血管内皮生长因子A(165)或增强型绿色荧光蛋白(EGFP)荧光素酶融合蛋白的质粒直接注入大鼠心脏。结果表明，基因表达与剂量相关，基因表达的持续时间是短暂的。这些发现强调了探索其他有效的载体或替代的基因传递方法以实现增加和延长基因表达的必要性。
Transfer of genes encoding therapeutic proteins into the myocardium shows great potential for treatment of coronary artery disease. To quantitatively elucidate the behavior of plasmid DNA following cardiac gene transfer, time kinetics, dose-response relationship, systemic spread to the liver, and the influence of different promoters on plasmid DNA gene expression in rat hearts were examined using a novel nonsurgical direct delivery method that enables testing of large numbers of animals. Plasmids encoding either vascular endothelial growth factor A(165) or a fusion protein between enhanced green fluorescent protein (EGFP) luciferase were injected directly in rat hearts under echocardiographic guidance. The results show that gene expression is dose related and that the duration of gene expression is transient. These findings underscore the necessity to explore other efficient vectors or alternative methods of gene delivery to achieve increased and prolonged gene expression.