Delivery systems for the direct application of siRNAs to induce RNA interference (RNAi) in vivo.
Delivery systems for the direct application of siRNAs to induce RNA interference (RNAi) in vivo.
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DOI：
10.1155/jbb/2006/71659
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发表时间：
2006
影响因子：
--
通讯作者：
Aigner, Achim
中科院分区：
文献类型：
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作者：
Aigner, Achim
RNA干扰（RNAi）是一种有效的特异性基因沉默方法，也可能导致有前途的新的治疗策略。它通过小干扰RNA（siRNA）介导，小干扰RNA序列特异性地触发其靶mRNA的切割和随后的降解。一个关键因素是在体内将完整siRNA递送到靶细胞/器官中的能力。本文综述了RNAi的作用机制以及设计最佳siRNA的指导原则。它概述了基于裸siRNA的全身或局部应用或各种非病毒siRNA递送系统的使用的研究。一种有希望的途径是siRNA与聚乙烯亚胺（PEI）的复合，其有效地稳定siRNA，并且在全身施用时，导致完整siRNA递送到不同器官中。描述了PEI/siRNA介导的肿瘤相关蛋白的体内基因靶向的抗肿瘤作用，如在小鼠肿瘤异种移植模型中。
RNA interference (RNAi) is a powerful method for specific gene silencing which may also lead to promising novel therapeutic strategies. It is mediated through small interfering RNAs (siRNAs) which sequence-specifically trigger the cleavage and subsequent degradation of their target mRNA. One critical factor is the ability to deliver intact siRNAs into target cells/organs in vivo. This review highlights the mechanism of RNAi and the guidelines for the design of optimal siRNAs. It gives an overview of studies based on the systemic or local application of naked siRNAs or the use of various nonviral siRNA delivery systems. One promising avenue is the the complexation of siRNAs with the polyethylenimine (PEI), which efficiently stabilizes siRNAs and, upon systemic administration, leads to the delivery of the intact siRNAs into different organs. The antitumorigenic effects of PEI/siRNA-mediated in vivo gene-targeting of tumor-relevant proteins like in mouse tumor xenograft models are described.