Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing's sarcoma
Sequence-specific knockdown of EWS-FLI1 by targeted, nonviral delivery of small interfering RNA inhibits tumor growth in a murine model of metastatic Ewing's sarcoma
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DOI：
10.1158/0008-5472.can-05-0565
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发表时间：
2005-10-01
期刊：
影响因子：
11.2
通讯作者：
Triche, TJ
中科院分区：
文献类型：
--
作者：
Hu-Lieskovan, S;Heidel, JD;Triche, TJ
开发有效的、系统的治疗转移性癌症的方法是非常必要的。我们在这里展示了通过靶向的非病毒递送系统针对EWS-FLI1基因产物的序列特异性小干扰RNA(ARNA)的系统递送显著地抑制了转移性尤文氏肉瘤小鼠模型的肿瘤生长。非病毒递送系统使用含有环糊精的聚阳离子结合和保护siRNA和转铁蛋白作为靶向配体，将其递送到转铁蛋白受体表达的肿瘤细胞。去除靶向配体或使用对照siRNA序列可消除抗肿瘤作用。此外，在长期、低压、低流量尾静脉给药中，没有观察到白细胞介素12和干扰素-α、肝和肾功能测试、完整血细胞计数或主要器官病理的异常。这些数据为这种靶向、非病毒的siRNA递送系统的安全性和有效性提供了强有力的证据。
The development of effective, systemic therapies for metastatic cancer is highly desired. We show here that the systemic delivery of sequence-specific small interfering RNA (ARNA) against the EWS-FLI1 gene product by a targeted, nonviral delivery system dramatically inhibits tumor growth in a murine model of metastatic Ewing's sarcoma. The nonviral delivery system uses a cyclodextrin-containing polycation to bind and protect siRNA and transferrin as a targeting ligand for delivery to transferrin receptor-expressing tumor cells. Removal of the targeting ligand or the use of a control siRNA sequence eliminates the antitumor effects. Additionally, no abnormalities in interleukin-12 and IFN-alpha, liver and kidney function tests, complete blood counts, or pathology of major organs are observed from long-term, low-pressure, low-volume tail-vein administrations. These data provide strong evidence for the safety and efficacy of this targeted, nonviral siRNA delivery system.