Conditionally replicating adenoviruses expressing short hairpin RNAs silence the expression of a target gene in cancer cells
Conditionally replicating adenoviruses expressing short hairpin RNAs silence the expression of a target gene in cancer cells
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DOI：
10.1158/0008-5472.can-03-3530
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发表时间：
2004-04-15
期刊：
影响因子：
11.2
通讯作者：
van Beusechem, VW
中科院分区：
文献类型：
--
作者：
Carette, JE;Overmeer, RM;van Beusechem, VW
RNA干扰（RNAi）是一种由双链RNA触发的转录后沉默机制，最近被证明在哺乳动物细胞中发挥作用。通过在癌细胞中表达短发夹RNA（shRNAs）来敲低癌症相关基因的表达。RNAi具有良好的靶向特异性，有望成为一种新的肿瘤治疗手段。这种方法的成功将在很大程度上取决于shRNA向肿瘤细胞的有效递送。具有肿瘤选择性复制能力的病毒特别适合于有效地将抗癌基因递送至肿瘤。此外，它们杀死癌细胞的内在能力使这些病毒本身成为有前途的抗癌剂。在这项研究中，条件复制腺病毒构建编码靶向萤火虫荧光素酶的shRNA。这些复制病毒显示出特异性沉默靶基因在人类癌细胞中的表达，相对于对照病毒降低至30%。这一发现为在溶瘤病毒的癌症基因治疗背景下使用RNAi提供了希望。
RNA interference (RNAi) is a posttranscriptional silencing mechanism triggered by double-stranded RNA that was recently shown to function in mammalian cells. Expression of cancer-associated genes was knocked down by expressing short hairpin RNAs (shRNAs) in cancer cells. By virtue of its excellent target specificity, RNAi may be used as a new therapeutic modality for cancer. The success of this approach will largely depend on efficient delivery of shRNAs to tumor cells. Tumor-selective replication competent viruses are especially suited to efficiently deliver anticancer genes to tumors. In addition, their intrinsic capacity to kill cancer cells makes these viruses promising anticancer agents per se. In this study, conditionally replicating adenoviruses were constructed encoding shRNAs targeted against firefly luciferase. These replicating viruses were shown to specifically silence the expression of the target gene in human cancer cells down to 30% relative to control virus. This finding offers the promise of using RNAi in the context of cancer gene therapy with oncolytic viruses.