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dc.contributor.authorZahaf , N.-I.en_US
dc.contributor.authorLang, A. E.en_US
dc.contributor.authorKaiser, L.en_US
dc.contributor.authorFichter, C. D.en_US
dc.contributor.authorLassmann, S.en_US
dc.contributor.authorMcCluskey, A.en_US
dc.contributor.authorAugspach, A.en_US
dc.contributor.authorAktories, K.en_US
dc.contributor.authorSchmidt, G.en_US
dc.date.accessioned2017-03-28T23:47:59Z
dc.date.issued2017en_US
dc.identifier.citationZahaf, N.-I., A. E. Lang, L. Kaiser, C. D. Fichter, S. Lassmann, A. McCluskey, A. Augspach, K. Aktories, and G. Schmidt. 2017. “Targeted delivery of an ADP-ribosylating bacterial toxin into cancer cells.” Scientific Reports 7 (1): 41252. doi:10.1038/srep41252. http://dx.doi.org/10.1038/srep41252.en
dc.identifier.issnen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:31731640
dc.description.abstractThe actin cytoskeleton is an attractive target for bacterial toxins. The ADP-ribosyltransferase TccC3 from the insect bacterial pathogen Photorhabdus luminescence modifies actin to force its aggregation. We intended to transport the catalytic part of this toxin preferentially into cancer cells using a toxin transporter (Protective antigen, PA) which was redirected to Epidermal Growth Factor Receptors (EGFR) or to human EGF receptors 2 (HER2), which are overexpressed in several cancer cells. Protective antigen of anthrax toxin forms a pore through which the two catalytic parts (lethal factor and edema factor) or other proteins can be transported into mammalian cells. Here, we used PA as a double mutant (N682A, D683A; mPA) which cannot bind to the two natural anthrax receptors. Each mutated monomer is fused either to EGF or to an affibody directed against the human EGF receptor 2 (HER2). We established a cellular model system composed of two cell lines representing HER2 overexpressing esophageal adenocarcinomas (EACs) and EGFR overexpressing esophageal squamous cell carcinomas (ESCCs). We studied the specificity and efficiency of the re-directed anthrax pore for transport of TccC3 toxin and established Photorhabdus luminescence TccC3 as a toxin suitable for the development of a targeted toxin selectively killing cancer cells.en
dc.language.isoen_USen
dc.publisherNature Publishing Groupen
dc.relation.isversionofdoi:10.1038/srep41252en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5269596/pdf/en
dash.licenseLAAen_US
dc.titleTargeted delivery of an ADP-ribosylating bacterial toxin into cancer cellsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalScientific Reportsen
dc.date.available2017-03-28T23:47:59Z
dc.identifier.doi10.1038/srep41252*
dash.authorsorderedfalse


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