Tsai Kun-Che, Liao Zhe-Kang, Yang Shu-Jyuan, Lin Win-Li, Shieh Ming-Jium, Hwang Lih-Hwa, Chen Wen-Shiang
Institute of Biomedical Engineering, National Taiwan University College of Medicine, Taipei 100, Taiwan.
J Gene Med. 2009 Oct;11(10):933-40. doi: 10.1002/jgm.1376.
Ultrasound (US) is a novel and effective tool for the local delivery of genes into target tissues. US can temporarily change the permeability of a cell membrane and thus enhance the delivery of naked DNA into cells. In the present study, the efficiencies of gene expression mediated by US delivery in orthotopic liver tumor, subcutaneous tumor and muscle tissue were evaluated by changing the contrast agent concentrations and US exposure durations.
Plasmid DNA coding for luciferase, interleukin-12 or enhanced green fluorescence protein was mixed with SonoVue and injected intratumorally or intramuscularly. The injection sites were then exposed to US (20% duty cycle and 0.4 W/cm(2) intensity).
The results obtained showed that the optimal condition was 50% SonoVue for tumors and 30% for muscle, with 10 min of US exposure. The expression levels of the transfected DNAs were in the order: muscle > subcutaneous tumor > orthotopic liver tumor.
The present study indicates that muscle tissue is a good target site for producing large amounts of gene products for the purpose of gene therapy.
超声（US）是一种将基因局部递送至靶组织的新型有效工具。超声可暂时改变细胞膜通透性，从而增强裸DNA进入细胞的递送效率。在本研究中，通过改变造影剂浓度和超声暴露时间，评估了超声递送介导的基因表达在原位肝肿瘤、皮下肿瘤和肌肉组织中的效率。
将编码荧光素酶、白细胞介素-12或增强型绿色荧光蛋白的质粒DNA与声诺维混合，进行瘤内或肌肉内注射。然后将注射部位暴露于超声（占空比20%，强度0.4W/cm²）。
结果表明，最佳条件为肿瘤使用50%声诺维，肌肉使用30%声诺维，超声暴露10分钟。转染DNA的表达水平顺序为：肌肉＞皮下肿瘤＞原位肝肿瘤。
本研究表明，肌肉组织是用于基因治疗目的生产大量基因产物的良好靶位点。
Zotero 插件