Photochemically induced gene silencing using small interfering RNA molecules in combination with lipid carriers
Photochemically induced gene silencing using small interfering RNA molecules in combination with lipid carriers
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DOI：
10.1089/oli.2007.0076
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发表时间：
2007-01-01
期刊：
影响因子：
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通讯作者：
Hovig, E.
中科院分区：
文献类型：
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作者：
Boe, S.;Longva, A. S.;Hovig, E.
RNA干扰（RNAi）疗法的发展需要有效递送具有靶向潜力的小干扰RNA（siRNA）分子的新策略。在这里，我们提出了一种策略，是基于通过内吞途径的siRNA分子的交付，以开发一种方法，位点特异性基因沉默。为了实现这一点，我们结合使用阳离子脂质和光化学内化（PCI）。使用人S100 A4基因作为模型系统，当使用阳离子脂质jetSI（TM）-ENDO时，我们在PCI诱导后的四种测试的人癌细胞系中获得有效的基因沉默。当使用jetSI（TM）试剂和优化的PCI方案时，在RNA和蛋白质水平均显示出基因沉默，并且没有观察到PCI毒性。这种新的诱导方法为siRNA分子向感兴趣的序列的体内位点特异性递送打开了大门。
Novel strategies for efficient delivery of small interfering RNA (siRNA) molecules with a potential for targeting are required for development of RNA interference (RNAi) therapeutics. Here, we present a strategy that is based on delivery of siRNA molecules through the endocytic pathway, in order to develop a method for site-specific gene silencing. To achieve this, we combined the use of cationic lipids and photochemical internalization (PCI). Using the human S100A4 gene as a model system, we obtained potent gene silencing in four tested human cancer cell lines following PCI induction when using the cationic lipid jetSI(TM) -ENDO. Gene silencing was shown at both the RNA and protein levels, with no observed PCI toxicity when using the jetSI(TM) reagent and an optimized PCI protocol. This novel induction method opens for in vivo site-specific delivery of siRNA molecules toward a sequence of interest.