Lipid-mediated siRNA delivery down-regulates exogenous gene expression in the mouse brain at picomolar levels
Lipid-mediated siRNA delivery down-regulates exogenous gene expression in the mouse brain at picomolar levels
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DOI：
10.1002/jgm.659
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发表时间：
2005-02-01
影响因子：
3.5
通讯作者：
Demeneix, BA
中科院分区：
文献类型：
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作者：
Hassani, Z;Lemkine, GF;Demeneix, BA
为了开发RNA干扰（RNAi）的巨大潜力，需要有效的体内载体。此类方法需要针对特定递送途径、组织和用途进行优化。我们测试了不同的非病毒载体和配制方法抑制外源性免疫缺陷病毒的能力。当用于将小干扰RNA（SiRNA）引入体内小鼠大脑时，（荧光素酶）基因表达。方法基于聚乙烯亚胺（PEI）的聚合物和JetSI（TM）（阳离子脂质的混合物）-基于脂质复合物的载体用于载体化编码萤火虫Photinuspyralis荧光素酶基因的质粒DNA和皮摩尔量的针对该基因的siRNA。结果首先，我们发现，线性PEI，虽然有效地将核酸传递到细胞，但在测试的剂量范围内不允许siRNA活性的发展（
Background Efficient in vivo vectors are needed to exploit the enormous potential of RNA interference (RNAi). Such methods require optimisation for specific delivery routes, tissues and usages. We tested the capacity of different non-viral vectors and formulation methods for inhibition of exogenous (luciferase) gene expression when used to introduce small interfering RNA (siRNA) into the mouse brain in vivo.Methods Polyethylenimine (PEI)-based polyplexes and JetSI(TM) (a mixture of cationic lipids)-based lipoplexes were used to vectorise plasmid DNA encoding the firefly Photinus pyralis luciferase gene and picomolar amounts of siRNA directed against this gene. Two controls were used, DNA encoding an unrelated luciferase from Renilla reniformis and a mutated siRNA sequence.Results First, we found that linear PEI, although efficient for delivering nucleic acids to cells, did not permit development of siRNA activity within the dose range tested (