RNA聚合酶Ⅱ启动子调控RNA干扰在肿瘤治疗中的应用前景  

Prospects of RNA Interference Induced by RNA Pol Ⅱ Promoter in Cancer Therapy

作　　者：陈青[1] 潘秋卫[1] 蔡荣[1] 钱程[1] 

机构地区：[1]浙江理工大学生命科学学院新元医学与生物技术研究所,杭州310018

出　　处：《生物化学与生物物理进展》2007年第8期806-815,共10页Progress In Biochemistry and Biophysics

基　　金：国家高技术研究发展计划(863)资助项目(2006AA02Z126);国家重点基础研究发展计划(973)(2004CB518804)资助项目.~~

摘　　要：RNA干扰是双链RNA介导的特异性转录后基因表达沉默现象.由于双链小干扰RNA介导的RNA干扰技术设计简便、作用迅速、效果明显,目前已被广泛应用于基因功能和重大疾病治疗的研究,尤其为肿瘤治疗提供了一条新途径.利用RNA干扰技术通过调节肿瘤发生发展相关基因的表达可制定出一系列有效的抗癌策略.然而在现行大多数策略中往往采用不可调控的RNA聚合酶Ⅲ启动子(H1,U6)表达经典的发夹结构RNA,经由Dicer酶切割成功能性siRNA,因此缺乏组织细胞靶向性和抗癌效率.最新研究表明,采用RNA聚合酶Ⅱ启动子可弥补由RNA聚合酶Ⅲ启动子调控RNA干扰缺陷和不足.此外,运用病毒载体特别是具有靶向和溶瘤效应的肿瘤特异性复制腺病毒,介导RNA聚合酶Ⅱ启动子调控表达siRNA有望成为更有效的治疗手段.RNA interference （RNAi） is a gene-silencing progress induced by double stranded RNA at a level of posttranscription. At present, RNAi has been extensively applied to the research domain of gene functions and disease therapies, especially for the therapy of malignant tumours due to its simple designs, immediate effects and obvious efficiency. Up to now, a number of novel strategies have been engineered to effectively fight against malignancies through RNAi technology in the regulation of the tumorigenesis-and-progression-associated genes. Presently, uncontrolled RNA Pol Ⅲ promoter expressing classical small hairpin RNA which can be processed into siRNA by Dicer enzyme is extensively applied. However, most of the current methods lack of tumor targeting and high efficiency in cancer therapy. The latest studies have demonstrated that RNAi induced by the tissue specific RNA Pol Ⅱpromoter could compensate for a deficiency of RNAi mediated by RNA Pol Ⅲ promoter. Moreover, virus vectors, especially cancer-specific replicable adenovirus targeting to cancer cells and oncolysising, which can express siRNA controlled by RNA Pol Ⅱ promoter, is expected to be a more effective therapy strategy.

关 键 词：RNA干扰 RNA聚合酶Ⅱ启动子 肿瘤治疗 

分 类 号：Q789[生物学—分子生物学]