001     136981
005     20240321220152.0
024 7 _ |a 10.1038/nbt.2612
|2 doi
024 7 _ |a pmid:23792630
|2 pmid
024 7 _ |a 0733-222X
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024 7 _ |a 1087-0156
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024 7 _ |a 1546-1696
|2 ISSN
024 7 _ |a 2331-3684
|2 ISSN
024 7 _ |a altmetric:1577822
|2 altmetric
037 _ _ |a DZNE-2020-03303
041 _ _ |a English
082 _ _ |a 660
100 1 _ |a Gilleron, Jerome
|0 P:(DE-HGF)0
|b 0
245 _ _ |a Image-based analysis of lipid nanoparticle-mediated siRNA delivery, intracellular trafficking and endosomal escape.
260 _ _ |a New York, NY
|c 2013
|b Nature America
264 _ 1 |3 online
|2 Crossref
|b Springer Science and Business Media LLC
|c 2013-06-23
264 _ 1 |3 print
|2 Crossref
|b Springer Science and Business Media LLC
|c 2013-07-01
336 7 _ |a article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a 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%) 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.
536 _ _ |a 342 - Disease Mechanisms and Model Systems (POF3-342)
|0 G:(DE-HGF)POF3-342
|c POF3-342
|f POF III
|x 0
542 _ _ |i 2013-06-23
|2 Crossref
|u http://www.springer.com/tdm
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a Lipids
|2 NLM Chemicals
650 _ 7 |a RNA, Small Interfering
|2 NLM Chemicals
650 _ 7 |a Green Fluorescent Proteins
|0 147336-22-9
|2 NLM Chemicals
650 _ 7 |a Gold
|0 7440-57-5
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Endocytosis: genetics
|2 MeSH
650 _ 2 |a Gene Transfer Techniques
|2 MeSH
650 _ 2 |a Gold: administration & dosage
|2 MeSH
650 _ 2 |a Gold: chemistry
|2 MeSH
650 _ 2 |a Green Fluorescent Proteins: antagonists & inhibitors
|2 MeSH
650 _ 2 |a Green Fluorescent Proteins: genetics
|2 MeSH
650 _ 2 |a HeLa Cells
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Lipids: administration & dosage
|2 MeSH
650 _ 2 |a Lipids: chemistry
|2 MeSH
650 _ 2 |a Lipids: genetics
|2 MeSH
650 _ 2 |a Metal Nanoparticles: administration & dosage
|2 MeSH
650 _ 2 |a Metal Nanoparticles: chemistry
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Microscopy, Electron
|2 MeSH
650 _ 2 |a RNA, Small Interfering: administration & dosage
|2 MeSH
650 _ 2 |a RNA, Small Interfering: chemistry
|2 MeSH
650 _ 2 |a RNA, Small Interfering: genetics
|2 MeSH
700 1 _ |a Querbes, William
|0 P:(DE-HGF)0
|b 1
700 1 _ |a Zeigerer, Anja
|0 P:(DE-HGF)0
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700 1 _ |a Borodovsky, Anna
|0 P:(DE-HGF)0
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700 1 _ |a Marsico, Giovanni
|0 P:(DE-HGF)0
|b 4
700 1 _ |a Schubert, Undine
|0 P:(DE-HGF)0
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700 1 _ |a Manygoats, Kevin
|0 P:(DE-HGF)0
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700 1 _ |a Seifert, Sarah
|0 P:(DE-HGF)0
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700 1 _ |a Andree, Cordula
|0 P:(DE-HGF)0
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700 1 _ |a Stöter, Martin
|0 P:(DE-HGF)0
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700 1 _ |a Epstein-Barash, Hila
|0 P:(DE-HGF)0
|b 10
700 1 _ |a Zhang, Ligang
|0 P:(DE-HGF)0
|b 11
700 1 _ |a Koteliansky, Victor
|0 P:(DE-HGF)0
|b 12
700 1 _ |a Fitzgerald, Kevin
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700 1 _ |a Fava, Eugenio
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|u dzne
700 1 _ |a Bickle, Marc
|0 P:(DE-HGF)0
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700 1 _ |a Kalaidzidis, Yannis
|0 P:(DE-HGF)0
|b 16
700 1 _ |a Akinc, Akin
|0 P:(DE-HGF)0
|b 17
700 1 _ |a Maier, Martin
|0 P:(DE-HGF)0
|b 18
700 1 _ |a Zerial, Marino
|0 P:(DE-HGF)0
|b 19
|e Corresponding author
773 1 8 |a 10.1038/nbt.2612
|b : Springer Science and Business Media LLC, 2013-06-23
|n 7
|p 638-646
|3 journal-article
|2 Crossref
|t Nature Biotechnology
|v 31
|y 2013
|x 1087-0156
773 _ _ |a 10.1038/nbt.2612
|g Vol. 31, no. 7, p. 638 - 646
|0 PERI:(DE-600)1494943-X
|n 7
|q 31:7<638 - 646
|p 638-646
|t Nature biotechnology
|v 31
|y 2013
|x 1087-0156
856 4 _ |u https://pub.dzne.de/record/136981/files/DZNE-2020-03303_Restricted.pdf
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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913 1 _ |a DE-HGF
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LibraryCollectionCLSMajorCLSMinorLanguageAuthor
Marc 21