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

被引：433
作者：
Hu-Lieskovan, S
Heidel, JD
Bartlett, DW
Davis, ME
Triche, TJ
机构：
[1] Childrens Hosp Los Angeles, Dept Pathol, Los Angeles, CA 90027 USA
[2] CALTECH, Pasadena, CA 91125 USA
来源：
CANCER RESEARCH | 2005年 / 65卷 / 19期
关键词：
D O I：
10.1158/0008-5472.CAN-05-0565
中图分类号：
R73 [肿瘤学];
学科分类号：
100214 ;
摘要：
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.
引用
收藏
页码：8984 / 8992
页数：9
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