Schneider, Anselm F. L. ; Kithil, Marina ; Cardoso, M. Cristina ; Lehmann, Martin ; Hackenberger, Christian P. R. (2021)
Cellular uptake of large biomolecules enabled by cell-surface-reactive cell-penetrating peptide additives.
In: Nature chemistry, 13 (6)
doi: 10.1038/s41557-021-00661-x
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
Enabling the cellular delivery and cytosolic bioavailability of functional proteins constitutes a major challenge for the life sciences. Here we demonstrate that thiol-reactive arginine-rich peptide additives can enhance the cellular uptake of protein-CPP conjugates in a non-endocytic mode, even at low micromolar concentration. We show that such thiol- or HaloTag-reactive additives can result in covalently anchored CPPs on the cell surface, which are highly effective at co-delivering protein cargoes. Taking advantage of the thiol reactivity of our most effective CPP additive, we show that Cys-containing proteins can be readily delivered into the cytosol by simple co-addition of a slight excess of this CPP. Furthermore, we demonstrate the application of our 'CPP-additive technique' in the delivery of functional enzymes, nanobodies and full-length immunoglobulin-G antibodies. This new cellular uptake protocol greatly simplifies both the accessibility and efficiency of protein and antibody delivery, with minimal chemical or genetic engineering.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2021 |
| Autor(en): | Schneider, Anselm F. L. ; Kithil, Marina ; Cardoso, M. Cristina ; Lehmann, Martin ; Hackenberger, Christian P. R. |
| Art des Eintrags: | Bibliographie |
| Titel: | Cellular uptake of large biomolecules enabled by cell-surface-reactive cell-penetrating peptide additives. |
| Sprache: | Englisch |
| Publikationsjahr: | 15 April 2021 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Nature chemistry |
| Jahrgang/Volume einer Zeitschrift: | 13 |
| (Heft-)Nummer: | 6 |
| DOI: | 10.1038/s41557-021-00661-x |
| Kurzbeschreibung (Abstract): | Enabling the cellular delivery and cytosolic bioavailability of functional proteins constitutes a major challenge for the life sciences. Here we demonstrate that thiol-reactive arginine-rich peptide additives can enhance the cellular uptake of protein-CPP conjugates in a non-endocytic mode, even at low micromolar concentration. We show that such thiol- or HaloTag-reactive additives can result in covalently anchored CPPs on the cell surface, which are highly effective at co-delivering protein cargoes. Taking advantage of the thiol reactivity of our most effective CPP additive, we show that Cys-containing proteins can be readily delivered into the cytosol by simple co-addition of a slight excess of this CPP. Furthermore, we demonstrate the application of our 'CPP-additive technique' in the delivery of functional enzymes, nanobodies and full-length immunoglobulin-G antibodies. This new cellular uptake protocol greatly simplifies both the accessibility and efficiency of protein and antibody delivery, with minimal chemical or genetic engineering. |
| ID-Nummer: | pmid:33859390 |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Cell Biology and Epigenetics |
| Hinterlegungsdatum: | 19 Apr 2021 12:52 |
| Letzte Änderung: | 27 Sep 2021 11:41 |
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