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  A ligand-based system for receptor-specific delivery of proteins

Maffei, M., Morelli, C., Graham, E., Patriarca, S., Donzelli, L., Doleschall, B., et al. (2019). A ligand-based system for receptor-specific delivery of proteins. Scientific Reports, 9(1): 19214, pp. 1-14. doi:10.1038/s41598-019-55797-1.

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Item Permalink: https://hdl.handle.net/21.11116/0000-0005-814E-2 Version Permalink: https://hdl.handle.net/21.11116/0000-0005-814F-1
Genre: Journal Article

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 Creators:
Maffei, Mariano, Author
Morelli, Chiara, Author
Graham, Ellie, Author
Patriarca, Stefano, Author
Donzelli, Laura, Author
Doleschall, Balint, Author
de Reis, Fernanda Castro, Author
Nocchi, Linda, Author
Chadick, Cora H., Author
Reymond, Luc, Author
Ivan R. , Corrêa Jr., Author
Johnsson, Kai1, Author           
Hackett, Jamie A., Author
Heppenstall, Paul A., Author
Affiliations:
1Chemical Biology, Max Planck Institute for Medical Research, Max Planck Society, ou_2364732              

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Free keywords: Biochemistry ; Biological techniques ; Biotechnology ; Cell biology ; Chemical biology ; Molecular biology
 Abstract: Gene delivery using vector or viral-based methods is often limited by technical and safety barriers. A promising alternative that circumvents these shortcomings is the direct delivery of proteins into cells. Here we introduce a non-viral, ligand-mediated protein delivery system capable of selectively targeting primary skin cells in-vivo. Using orthologous self-labelling tags and chemical cross-linkers, we conjugate large proteins to ligands that bind their natural receptors on the surface of keratinocytes. Targeted CRE-mediated recombination was achieved by delivery of ligand cross-linked CRE protein to the skin of transgenic reporter mice, but was absent in mice lacking the ligand's cell surface receptor. We further show that ligands mediate the intracellular delivery of Cas9 allowing for CRISPR-mediated gene editing in the skin more efficiently than adeno-associated viral gene delivery. Thus, a ligand-based system enables the effective and receptor-specific delivery of large proteins and may be applied to the treatment of skin-related genetic diseases.

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Language(s): eng - English
 Dates: 2019-08-132019-10-302019-12-16
 Publication Status: Published online
 Pages: 14
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/s41598-019-55797-1
URI: https://www.ncbi.nlm.nih.gov/pubmed/31844114
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Title: Scientific Reports
  Abbreviation : Sci. Rep.
Source Genre: Journal
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Publ. Info: London, UK : Nature Publishing Group
Pages: - Volume / Issue: 9 (1) Sequence Number: 19214 Start / End Page: 1 - 14 Identifier: ISSN: 2045-2322
CoNE: https://pure.mpg.de/cone/journals/resource/2045-2322