Atelocollagen-mediated synthetic small interfering RNA delivery for effective gene silencing in vitro and in vivo -: art. no. e109
Atelocollagen-mediated synthetic small interfering RNA delivery for effective gene silencing in vitro and in vivo -: art. no. e109
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DOI：
10.1093/nar/gnh093
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发表时间：
2004-01-01
影响因子：
14.9
通讯作者：
Ochiya, T
中科院分区：
文献类型：
--
作者：
Minakuchi, Y;Takeshita, F;Ochiya, T
通过sirna沉默基因表达正迅速成为哺乳动物细胞遗传分析的有力工具。然而，siRNA的快速降解及其作用时间有限，需要一种有效的递送技术。因此，我们在这里描述了与si RNA复合物的atelocolagen对核酸酶具有抗性，并有效地转导到细胞中，从而允许长期的基因沉默。抗荧光素酶siRNA/ atelocolen复合物的体内部位特异性管理降低了异种移植肿瘤中荧光素酶的表达。此外，在人非半胱氨酸生殖细胞肿瘤的原位异种移植模型中，胶原介导的siRNA在体内的转移显示出有效的肿瘤生长抑制。因此，对于siRNA的临床应用，基于atelocolcollagen的非病毒递送方法可能是实现siRNA在体内最大功能的可靠途径。
Silencing gene expression by siRNAs is rapidly becoming a powerful tool for the genetic analysis of mammalian cells. However, the rapid degradation of siRNA and the limited duration of its action call for an efficient delivery technology. Accordingly, we describe here that Atelocollagen complexed with si RNA is resistant to nucleases and is efficiently transduced into cells, thereby allowing long-term gene silencing. Site-specific in vivo administration of an anti-luciferase siRNA/Atelocollagen complex reduced luciferase expression in a xenografted tumor. Furthermore, Atelocollagen-mediated transfer of siRNA in vivo showed efficient inhibition of tumor growth in an orthotopic xenograft model of a human non-seminomatous germ cell tumor. Thus, for clinical applications of siRNA, an Atelocollagen-based nonviral delivery method could be a reliable approach to achieve maximal function of siRNA in vivo.