Electroporation-mediated gene transfer directly to the swine heart.

Electroporation-mediated gene transfer directly to the swine heart.
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DOI:
10.1038/gt.2012.15
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发表时间:
2013-02
期刊:
影响因子:
5.1
通讯作者:
--
中科院分区:
医学3区
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--
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通过电穿孔向缺血心脏的体内基因转移有望成为治疗心脏病的潜在治疗方法。在当前的研究中,我们研究了使用3种不同的穿透电极和一种非穿透电极进行体内电穿孔基因转移。通过胸骨切开术暴露成年雄性猪的心脏。在注射编码荧光素酶的质粒或编码绿色荧光蛋白的质粒后,以不同的脉冲宽度和场强施用与ECG的R波的上升相同步的八个电脉冲。治疗了左心室前壁的4个部位。注射后48小时将动物安乐死,并测定电穿孔和基因表达。将结果与接受质粒注射但没有电脉冲或没有治疗的心脏部位进行比较。当与仅注射位点相比时,在所有电穿孔位点中的基因表达更高,证明了该方法的稳健性。我们的研究结果提供了证据,体内电穿孔可以是一种安全有效的非病毒方法,用于将基因传递到心脏,在体内。
In vivo gene transfer to the ischemic heart via electroporation holds promise as a potential therapeutic approach for the treatment of heart disease. In the current study, we investigated the use of in vivo electroporation for gene transfer using 3 different penetrating electrodes and one non-penetrating electrode. The hearts of adult male swine were exposed through a sternotomy. Eight electric pulses synchronized to the rising phase of the R wave of the ECG were administered at varying pulse widths and field strengths following an injection of either a plasmid encoding luciferase or one encoding green fluorescent protein. Four sites on the anterior wall of the left ventricle were treated. Animals were euthanized 48 hours after injection and electroporation and gene expression was determined. Results were compared to sites in the heart that received plasmid injection but no electric pulses or were not treated. Gene expression was higher in all electroporated sites when compared to injection only sites demonstrating the robustness of this approach. Our results provide evidence that in vivo electroporation can be a safe and effective non-viral method for delivering genes to the heart, in vivo.
DOI: 10.1152/ajpheart.1994.266.4.h1588
发表时间: 1994-04-01
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