Ultrasound enhances gene expression of asialoglycoprotein receptor medieted gene transfer into hepatic cells

超声增强脱唾液酸糖蛋白受体的基因表达介导的基因转移至肝细胞

• 批准号: 13670562
• 负责人: MORITASU Fuminori
• 金额: $ 2.3万
• 依托单位: Tokyo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670562/
• 关键词: Gene transfer; ultrasound; Asiologlycoprotein receptor; 遺伝子遺入

The aim of this study is to evaluate the effect of ultrasound on gene expression of asialoglycoprotein receptor-mediated gene transfer into hepatic cells. A plasmid vector carrying luciferase gene under SV40 promoter (PGV-C2) or cyclin A promoter was condensed with poly-lysine, and encapsulated into anionic asialofetuin-labeled liposome (AF-liposome). These complex was transfected to HepG2 cells, human hepatoblastomacell line. Optimal time intervals for application of ultrasound appear 1 hours after transfection. Optimal timeduration of ultrasound exposure was 30 seconds. Ultrasound of high duty cycle enhanced gene expression than that of low duty cycle. In these conditon, gene expression increased twice by ultrasound. This method may provide a novel transfection approach to liver disease, including liver tumor.

本研究的目的是评价超声对去唾液酸糖蛋白受体介导的基因转移到肝细胞中的基因表达的影响。将SV 40启动子（PGV-C2）或细胞周期蛋白A（cyclin A）启动子下的荧光素酶基因的质粒载体与多聚赖氨酸（poly-lysine）缩合，并包封于阴离子去唾液酸胎球蛋白标记的脂质体（AF-liposome）中。将此复合物转染人肝母细胞瘤细胞系HepG 2细胞。应用超声的最佳时间间隔出现在转染后1小时。最佳超声照射时间为30秒。高占空比的超声比低占空比的超声更能促进基因表达。在此条件下，超声可使基因表达增加两倍。该方法可能为肝脏疾病，包括肝肿瘤的治疗提供一种新的转染途径。

项目成果

Aramaki Y, Lee I, Arima R Sakamoto T, MagamiY, Yoshirnoto T, Mizuguchi J, Moriyasu F, KoyanagiY, Nikaido T, Tsuchiya S: "Efficient Gene Transferto Hepatoblastoma Cells through AsialoglycoproteinReceptor and Expression under the Control of theCyclin A Prom

Aramaki Y、Lee I、Arima R Sakamoto T、MagamiY、Yoshirnoto T、Mizuguchi J、Moriyasu F、KoyanagiY、Nikaido T、Tsuchiya S：“通过 Asialo 糖蛋白受体和在细胞周期蛋白 A Prom 控制下的表达，将基因有效转移至肝母细胞瘤细胞

MatsumuraT, Moriyasu F, Toda Y, Kishi K,Chiba T, Tabata: "Ultrasound exposureenhances thebiological action of interferon in the liver"Journal of Drug Targeting. 10(3). 205-209 (2002)

MatsumuraT、Moriyasu F、Toda Y、Kishi K、Chiba T、Tabata：“超声暴露增强干扰素在肝脏中的生物作用”药物靶向杂志。

Suginoshita Y, Tabata Y, Matsumura T, Toda Y,Nabeshijna M , Moriyasu F, Ikada Y, Chiba T: "Liver targeting of human interferon-beta with pullulan based onmetal coordination"J Control Release. 18; 83(1). 75-88 (2002)

Suginoshita Y、Tabata Y、Matsumura T、Toda Y、Nabeshijna M、Moriyasu F、Ikada Y、Chiba T：“基于金属协调的普鲁兰多糖对人类干扰素 β 的肝脏靶向”J Control Release。

Moriyasu F et al.: "Harmonic gray scale 3D contrast imaging of liver"Academic Radiology. 9. 228-230 (2002)

Moriyasu F 等人：“肝脏的谐波灰度 3D 对比成像”学术放射学。

Matsumura T et al.: "Ultrasound exposure enhances the biological action of interferon in the liver"J Drug Targeting. 10. 205-209 (2002)

Matsumura T 等人：“超声暴露增强干扰素在肝脏中的生物作用”J Drug Targeting。