Highly efficient electro-gene therapy of solid tumor by using an expression plasmid for the herpes simplex virus thymidine kinase gene

Highly efficient electro-gene therapy of solid tumor by using an expression plasmid for the herpes simplex virus thymidine kinase gene
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DOI:
10.1073/pnas.97.1.354
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发表时间:
2000-01-04
影响因子:
11.1
通讯作者:
Ushio, Y
Ushio, Y
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Goto, T;Nishi, T;Ushio, Y

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我们报道利用质粒DNA成功地对荷瘤小鼠进行电基因治疗(ECT)。皮下接种的CT26肿瘤进行ECT治疗,其中包括在瘤内注射编码标记基因或治疗基因的裸质粒,然后在体内电穿孔(EP)。当用绿色荧光蛋白基因的质粒DNA进行这种处理方式,然后用优化的脉冲参数进行体内EP处理时,肿瘤内出现了许多强烈明亮的绿色荧光信号。ECT通过使用白喉毒素基因的“A”片段,显著抑制小鼠侧腹肿瘤生长,抑制幅度约为30%。使用单纯疱疹病毒胸苷激酶基因,然后全身注射更昔洛韦,EGT在延缓肿瘤生长方面比其他对照组更有效,差异在50%到90%之间。基于这些结果,ECT似乎可以成功地用于治疗小鼠实体瘤。
We report successful electro-gene therapy (ECT) by using plasmid DNA for tumor-bearing mice. Subcutaneously inoculated CT26 tumor was subjected to ECT, which consists of intratumoral injection of a naked plasmid encoding a marker gene or a therapeutic gene, followed by in vivo electroporation (EP). When this treatment modality is carried out with the plasmid DNA for the green fluorescent protein gene, followed by in vivo EP with the optimized pulse parameters, numerous intensely bright green fluorescent signals appeared within the tumor. ECT, by using the "A" fragment of the diphtheria toxin gene significantly inhibited the growth of tumors, by about 30%, on the flank of mice. With the herpes simplex virus thymidine kinase gene, followed by systemic injection of ganciclovir, EGT was far more effective in retarding tumor growth, varying between 50% and 90%, compared with the other controls. Based on these results, it appears that ECT can be used successfully for treating murine solid tumors.