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@ARTICLE{Gilleron:136981,
      author       = {Gilleron, Jerome and Querbes, William and Zeigerer, Anja
                      and Borodovsky, Anna and Marsico, Giovanni and Schubert,
                      Undine and Manygoats, Kevin and Seifert, Sarah and Andree,
                      Cordula and Stöter, Martin and Epstein-Barash, Hila and
                      Zhang, Ligang and Koteliansky, Victor and Fitzgerald, Kevin
                      and Fava, Eugenio and Bickle, Marc and Kalaidzidis, Yannis
                      and Akinc, Akin and Maier, Martin and Zerial, Marino},
      title        = {{I}mage-based analysis of lipid nanoparticle-mediated
                      si{RNA} delivery, intracellular trafficking and endosomal
                      escape.},
      journal      = {Nature biotechnology},
      volume       = {31},
      number       = {7},
      issn         = {1087-0156},
      address      = {New York, NY},
      publisher    = {Nature America},
      reportid     = {DZNE-2020-03303},
      pages        = {638-646},
      year         = {2013},
      abstract     = {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.},
      keywords     = {Animals / Endocytosis: genetics / Gene Transfer Techniques
                      / Gold: administration $\&$ dosage / Gold: chemistry / Green
                      Fluorescent Proteins: antagonists $\&$ inhibitors / Green
                      Fluorescent Proteins: genetics / HeLa Cells / Humans /
                      Lipids: administration $\&$ dosage / Lipids: chemistry /
                      Lipids: genetics / Metal Nanoparticles: administration $\&$
                      dosage / Metal Nanoparticles: chemistry / Mice / Microscopy,
                      Electron / RNA, Small Interfering: administration $\&$
                      dosage / RNA, Small Interfering: chemistry / RNA, Small
                      Interfering: genetics / Lipids (NLM Chemicals) / RNA, Small
                      Interfering (NLM Chemicals) / Green Fluorescent Proteins
                      (NLM Chemicals) / Gold (NLM Chemicals)},
      cin          = {AG Fava 1},
      ddc          = {660},
      cid          = {I:(DE-2719)1013016},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:23792630},
      doi          = {10.1038/nbt.2612},
      url          = {https://pub.dzne.de/record/136981},
}