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000136981 0247_ $$2ISSN$$a2331-3684
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000136981 041__ $$aEnglish
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000136981 1001_ $$0P:(DE-HGF)0$$aGilleron, Jerome$$b0
000136981 245__ $$aImage-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape.
000136981 260__ $$aNew York, NY$$bNature America$$c2013
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000136981 520__ $$aDelivery of short interfering RNAs (siRNAs) remains a key challenge in the development of RNA interference (RNAi) therapeutics. A better understanding of the mechanisms of siRNA cellular uptake, intracellular transport and endosomal release could critically contribute to the improvement of delivery methods. Here we monitored the uptake of lipid nanoparticles (LNPs) loaded with traceable siRNAs in different cell types in vitro and in mouse liver by quantitative fluorescence imaging and electron microscopy. We found that LNPs enter cells by both constitutive and inducible pathways in a cell type-specific manner using clathrin-mediated endocytosis as well as macropinocytosis. By directly detecting colloidal-gold particles conjugated to siRNAs, we estimated that escape of siRNAs from endosomes into the cytosol occurs at low efficiency (1-2%) and only during a limited window of time when the LNPs reside in a specific compartment sharing early and late endosomal characteristics. Our results provide insights into LNP-mediated siRNA delivery that can guide development of the next generation of delivery systems for RNAi therapeutics.
000136981 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000136981 542__ $$2Crossref$$i2013-06-23$$uhttp://www.springer.com/tdm
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000136981 650_7 $$2NLM Chemicals$$aLipids
000136981 650_7 $$2NLM Chemicals$$aRNA, Small Interfering
000136981 650_7 $$0147336-22-9$$2NLM Chemicals$$aGreen Fluorescent Proteins
000136981 650_7 $$07440-57-5$$2NLM Chemicals$$aGold
000136981 650_2 $$2MeSH$$aAnimals
000136981 650_2 $$2MeSH$$aEndocytosis: genetics
000136981 650_2 $$2MeSH$$aGene Transfer Techniques
000136981 650_2 $$2MeSH$$aGold: administration & dosage
000136981 650_2 $$2MeSH$$aGold: chemistry
000136981 650_2 $$2MeSH$$aGreen Fluorescent Proteins: antagonists & inhibitors
000136981 650_2 $$2MeSH$$aGreen Fluorescent Proteins: genetics
000136981 650_2 $$2MeSH$$aHeLa Cells
000136981 650_2 $$2MeSH$$aHumans
000136981 650_2 $$2MeSH$$aLipids: administration & dosage
000136981 650_2 $$2MeSH$$aLipids: chemistry
000136981 650_2 $$2MeSH$$aLipids: genetics
000136981 650_2 $$2MeSH$$aMetal Nanoparticles: administration & dosage
000136981 650_2 $$2MeSH$$aMetal Nanoparticles: chemistry
000136981 650_2 $$2MeSH$$aMice
000136981 650_2 $$2MeSH$$aMicroscopy, Electron
000136981 650_2 $$2MeSH$$aRNA, Small Interfering: administration & dosage
000136981 650_2 $$2MeSH$$aRNA, Small Interfering: chemistry
000136981 650_2 $$2MeSH$$aRNA, Small Interfering: genetics
000136981 7001_ $$0P:(DE-HGF)0$$aQuerbes, William$$b1
000136981 7001_ $$0P:(DE-HGF)0$$aZeigerer, Anja$$b2
000136981 7001_ $$0P:(DE-HGF)0$$aBorodovsky, Anna$$b3
000136981 7001_ $$0P:(DE-HGF)0$$aMarsico, Giovanni$$b4
000136981 7001_ $$0P:(DE-HGF)0$$aSchubert, Undine$$b5
000136981 7001_ $$0P:(DE-HGF)0$$aManygoats, Kevin$$b6
000136981 7001_ $$0P:(DE-HGF)0$$aSeifert, Sarah$$b7
000136981 7001_ $$0P:(DE-HGF)0$$aAndree, Cordula$$b8
000136981 7001_ $$0P:(DE-HGF)0$$aStöter, Martin$$b9
000136981 7001_ $$0P:(DE-HGF)0$$aEpstein-Barash, Hila$$b10
000136981 7001_ $$0P:(DE-HGF)0$$aZhang, Ligang$$b11
000136981 7001_ $$0P:(DE-HGF)0$$aKoteliansky, Victor$$b12
000136981 7001_ $$0P:(DE-HGF)0$$aFitzgerald, Kevin$$b13
000136981 7001_ $$0P:(DE-2719)2159508$$aFava, Eugenio$$b14$$udzne
000136981 7001_ $$0P:(DE-HGF)0$$aBickle, Marc$$b15
000136981 7001_ $$0P:(DE-HGF)0$$aKalaidzidis, Yannis$$b16
000136981 7001_ $$0P:(DE-HGF)0$$aAkinc, Akin$$b17
000136981 7001_ $$0P:(DE-HGF)0$$aMaier, Martin$$b18
000136981 7001_ $$0P:(DE-HGF)0$$aZerial, Marino$$b19$$eCorresponding author
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