一种嵌合型调控元件在肿瘤靶向基因治疗中的应用  

An Integrated Gene Regulatory Element for Tumor-specific Targeting Therapy

作　　者：周培杰[1] 高维强[1,2] 方煜翔[1] 

机构地区：[1]上海交通大学医学院附属仁济医院仁济-MedX临床干细胞研究中心癌基因及相关基因国家重点实验室,上海200127 [2]上海交通大学生物医学工程学院,上海200030

出　　处：《生物技术通报》2015年第10期255-262,共8页Biotechnology Bulletin

基　　金：国家自然科学基金项目(81301857;81130038)

摘　　要：肿瘤靶向基因治疗成功的关键是调控治疗基因在肿瘤细胞中特异、高效地表达。首次构建一种嵌合型表达调控元件,旨在转录水平、转录后水平和翻译水平上实现联合调控目的基因在肿瘤细胞中特异性表达。体外实验表明,在前列腺癌细胞系LNCa P中,该调控元件可将报告基因增强型绿色荧光蛋白(EGFP)和荧光素酶(luciferase)的肿瘤表达特异性分别提高420%和480%。体外细胞存活实验表明,运用该元件调控单纯疱疹病毒-1胸腺激酶(HSV-1 TK)的表达能特异性杀伤LNCa P细胞,验证了该元件可成功用于治疗基因的肿瘤靶向表达。The key for a successful tumor-specific gene therapy is to regulate the therapeutic gene specifically and efficiently expressing in tumor cells. By the construction of an embedded expression regulatory element, a high efficiency as well as tumor-specific expression of target genes in tumor cells was achieved by integrated regulation at transcriptional, post-transcriptional and translational levels simultaneously. It was shown that the integrated gene regulatory element improved expressional specificities in prostate cancer cell line LNCa P up to 420% and 480% using enhanced green fluorescent protein（EGFP）and luciferase as reporter gene respectively in vitro. By survival assay in vitro, LNCa P cell survival was specifically suppressed by HSV-1 TK expression under the control of this regulator. These results confirmed that this element could be applied in tumor-specific targeting therapy.

关 键 词：肿瘤靶向基因治疗 嵌合型表达调控条件 绿色荧光蛋白 单纯疱疹病毒-1胸腺激酶 前列腺癌 

分 类 号：R730.5[医药卫生—肿瘤]