Electrically mediated delivery of vector plasmid DNA elicits an antitumor effect
Electrically mediated delivery of vector plasmid DNA elicits an antitumor effect
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DOI：
10.1038/sj.gt.3301802
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发表时间：
2002-10-01
期刊：
影响因子：
5.1
通讯作者：
Coppola, D
中科院分区：
文献类型：
--
作者：
Heller, L;Coppola, D
体内电穿孔是增加质粒DNA递送至正常组织（如皮肤和肌肉）以及直接递送至肿瘤的有效手段。在这里描述的实验中，使用两种非常不同的脉冲方案通过体内电穿孔将质粒DNA递送至B16小鼠黑素瘤。报告基因表达增加21或42倍，分别与单独注射电穿孔。在电穿孔递送报告质粒DNA后，监测治疗当天直径约为4mm的实验性黑素瘤的生长。值得注意的是，使用这些脉冲方案之一的短期完全消退发生在高达100%的小鼠中。这些退化在高达83%的动物中持续了很长时间。这些小鼠中的70%对B16黑素瘤细胞的攻击具有抗性。组织学分析显示处理后24小时大量凋亡细胞。这种抗肿瘤作用不需要治疗性cDNA表达或真核序列。
In vivo electroporation is an efficient means of increasing plasmid DNA delivery to normal tissues, such as skin and muscle, as well as directly to tumors. In the experiments described here, plasmid DNA was delivered by in vivo electroporation to B16 mouse melanomas using two very different pulsing protocols. Reporter expression increased 21- or 42-fold, respectively with electroporation over injection alone. The growth of experimental melanomas with an approximate diameter of 4 mm on the day of treatment was monitored after electroporation delivery of reporter plasmid DNA. Remarkably, short-term complete regressions using one of these pulsing protocols occurred in up to 100% of mice. These regressions continued long term in up to 83% of animals. 70% of these mice were resistant to challenge with B16 melanoma cells. Histological analysis revealed large numbers of apoptotic cells 24 h after treatment. This antitumor effect did not require therapeutic cDNA expression or eukaryotic sequences.