Carette Jan E, Overmeer Renée M, Schagen Frederik H E, Alemany Ramon, Barski Oleg A, Gerritsen Winald R, Van Beusechem Victor W
Division of Gene Therapy, Department of Medical Oncology, VU University Medical Center, Amsterdam, The Netherlands.
Cancer Res. 2004 Apr 15;64(8):2663-7. doi: 10.1158/0008-5472.can-03-3530.
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.
RNA干扰（RNAi）是一种由双链RNA触发的转录后沉默机制，最近研究表明其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（shRNA），可使癌症相关基因的表达受到抑制。凭借其出色的靶标特异性，RNAi有望成为一种新型癌症治疗方法。该方法的成功很大程度上取决于shRNA能否有效地递送至肿瘤细胞。肿瘤选择性复制型病毒特别适合于将抗癌基因高效递送至肿瘤。此外，它们固有的杀死癌细胞的能力使这些病毒本身就有望成为抗癌药物。在本研究中，构建了编码针对萤火虫荧光素酶的shRNA的条件性复制腺病毒。这些复制型病毒在人类癌细胞中能使靶基因的表达相对于对照病毒特异性沉默至30%。这一发现为将RNAi应用于溶瘤病毒介导的癌症基因治疗带来了希望。
