A peptidomimetic siRNA transfection reagent for highly effective gene silencing
A peptidomimetic siRNA transfection reagent for highly effective gene silencing
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DOI：
10.1039/b603229j
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发表时间：
2006-06-01
影响因子：
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通讯作者：
Kirshenbaum, Kent
中科院分区：
文献类型：
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作者：
Utku, Yeliz;Dehan, Elinor;Kirshenbaum, Kent
RNA干扰（RNAi）技术为治疗性沉默有害基因带来了巨大的希望。然而，RNAi的临床应用需要开发用于细胞内递送特异于靶基因的小干扰RNA（siRNA）寡核苷酸的安全且有效的方法。我们描述了类脂质（一种阳离子类寡肽-磷脂缀合物）在细胞培养中用于合成siRNA寡核苷酸的非病毒转染的用途。这种肽模拟物递送载体允许在多种人细胞系中进行有效的siRNA转染，毒性可忽略不计，并促进靶基因在蛋白质和mRNA水平上的广泛下调。我们将类脂质试剂与标准商业转染试剂进行比较。类脂质即使在其他商业试剂通常无效的原代IMR-90人肺成纤维细胞中也是高效的。
RNA interference (RNAi) techniques hold forth great promise for therapeutic silencing of deleterious genes. However, clinical applications of RNAi require the development of safe and efficient methods for intracellular delivery of small interfering RNA (siRNA) oligonucleotides specific to targeted genes. We describe the use of a lipitoid, a cationic oligopeptoid-phospholipid conjugate, for non-viral transfection of synthetic siRNA oligos in cell culture. This peptidomimetic delivery vehicle allows for efficient siRNA transfection in a variety of human cell lines with negligible toxicity and promotes extensive downregulation of the targeted genes at both the protein and the mRNA level. We compare the lipitoid reagent to a standard commercial transfection reagent. The lipitoid is highly efficient even in primary IMR-90 human lung fibroblasts in which other commercial reagents are typically ineffective.