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Cellular uptake of large biomolecules enabled by cell-surface-reactive cell-penetrating peptide additives.

Schneider, Anselm F. L. and Kithil, Marina and Cardoso, M. Cristina and Lehmann, Martin and Hackenberger, Christian P. R. (2021):
Cellular uptake of large biomolecules enabled by cell-surface-reactive cell-penetrating peptide additives.
In: Nature chemistry, ISSN 1755-4349,
DOI: 10.1038/s41557-021-00661-x,
[Article]

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.

Item Type: Article
Erschienen: 2021
Creators: Schneider, Anselm F. L. and Kithil, Marina and Cardoso, M. Cristina and Lehmann, Martin and Hackenberger, Christian P. R.
Title: Cellular uptake of large biomolecules enabled by cell-surface-reactive cell-penetrating peptide additives.
Language: English
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.

Journal or Publication Title: Nature chemistry
Divisions: 10 Department of Biology
10 Department of Biology > Cell Biology and Epigenetics
Date Deposited: 19 Apr 2021 12:52
DOI: 10.1038/s41557-021-00661-x
Identification Number: pmid:33859390
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