%0 Journal Article
%A Gilleron, Jerome
%A Querbes, William
%A Zeigerer, Anja
%A Borodovsky, Anna
%A Marsico, Giovanni
%A Schubert, Undine
%A Manygoats, Kevin
%A Seifert, Sarah
%A Andree, Cordula
%A Stöter, Martin
%A Epstein-Barash, Hila
%A Zhang, Ligang
%A Koteliansky, Victor
%A Fitzgerald, Kevin
%A Fava, Eugenio
%A Bickle, Marc
%A Kalaidzidis, Yannis
%A Akinc, Akin
%A Maier, Martin
%A Zerial, Marino
%T Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape.
%J Nature biotechnology
%V 31
%N 7
%@ 1087-0156
%C New York, NY
%I Nature America
%M DZNE-2020-03303
%P 638-646
%D 2013
%X Delivery 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
%K Animals
%K Endocytosis: genetics
%K Gene Transfer Techniques
%K Gold: administration & dosage
%K Gold: chemistry
%K Green Fluorescent Proteins: antagonists & inhibitors
%K Green Fluorescent Proteins: genetics
%K HeLa Cells
%K Humans
%K Lipids: administration & dosage
%K Lipids: chemistry
%K Lipids: genetics
%K Metal Nanoparticles: administration & dosage
%K Metal Nanoparticles: chemistry
%K Mice
%K Microscopy, Electron
%K RNA, Small Interfering: administration & dosage
%K RNA, Small Interfering: chemistry
%K RNA, Small Interfering: genetics
%K Lipids (NLM Chemicals)
%K RNA, Small Interfering (NLM Chemicals)
%K Green Fluorescent Proteins (NLM Chemicals)
%K Gold (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:23792630
%R 10.1038/nbt.2612
%U https://pub.dzne.de/record/136981