Steroid and lipid conjugates of siRNAs to enhance cellular uptake and gene silencing in liver cells

被引：263

作者：

Lorenz, C

Hadwiger, P

John, M

Vornlocher, HP

Unverzagt, C

机构：

[1] Alnylam Europe AG, D-95326 Kulmbach, Germany

[2] Univ Bayreuth, Lehrstuhl Bioorgan Chem, D-95440 Bayreuth, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2004年 / 14卷 / 19期

关键词：

siRNA; RNAi; cellular uptake; solid phase synthesis;

D O I：

10.1016/j.bmcl.2004.07.018

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Double-stranded short interfering RNAs (siRNAs) mediate post-transcriptional inhibition of gene expression in a variety of biological systems. However, human liver cells show poor uptake of these nucleic acids. In order to improve the delivery of siRNA into these cells without transfection agents, we have synthesized two series of lipophilic siRNAs conjugated with derivatives of cholesterol, lithocholic acid or lauric acid. The lipid moieties were covalently linked to the 5'-ends of the RNAs using phosphoramidite chemistry. The potency of these chemically modified siRNAs to inhibit reporter gene expression was further investigated in vitro with beta-galactosidase expressing liver cells. (C) 2004 Elsevier Ltd. All rights reserved.

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收藏

页码：4975 / 4977

页数：3

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