RNA interference in the mouse vascular endothelium by systemic administration of siRNA-lipoplexes for cancer therapy

被引：151

作者：

Santel, A. ^{[1
]}

Aleku, M. ^{[1
]}

Keil, O. ^{[1
]}

Endruschat, J. ^{[1
]}

Esche, V. ^{[1
]}

Durieux, B. ^{[1
]}

Loffler, K. ^{[1
]}

Fechtner, M. ^{[1
]}

Rohl, T. ^{[1
]}

Fisch, G. ^{[1
]}

Dames, S. ^{[1
]}

Arnold, W. ^{[1
]}

Giese, K. ^{[1
]}

Klippel, A. ^{[1
]}

Kaufmann, J. ^{[1
]}

机构：

[1] Atugen AG SR Pharma Plc Subsidiary, D-13125 Berlin, Germany

来源：

GENE THERAPY | 2006年 / 13卷 / 18期

关键词：

tumor vasculature; siRNA; angiogenesis; RNAi-based therapeutics; cationic liposomes;

D O I：

10.1038/sj.gt.3302778

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

RNA interference (RNAi) entails the potential for novel therapeutic strategies through the silencing of disease-causing genes in vivo. However, recent studies have raised an issue regarding applicable routes of administration for small interfering RNA ( siRNA) molecules as therapeutics. In this study, we demonstrate that liposomally formulated siRNA molecules, the so-called siRNA-lipoplexes, but not naked siRNAs, are delivered to the tumor endothelial cells in vivo by microscopy. In addition, functional intracellular delivery of formulated siRNA targeting the tumor suppressor PTEN is shown in endothelial cells of the liver and tumor. Finally, the therapeutic potential of systemically administered siRNA(CD31)-lipoplexes is established by inhibition of tumor growth in two different xenograft mouse models. Our findings corroborate the applicability of this liposomal siRNA delivery technology for inducing RNAi to modulate gene expression levels in angiogenesis-dependent processes. In addition, our results advocate CD31 as a promising therapeutic target for antiangiogenic intervention. Therefore, our study provides a basis for the development of antiangiogenic cancer therapies based on RNAi.

引用

页码：1360 / 1370

页数：11

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