Novel cell-penetrating peptide-adaptors effect intracellular delivery and endosomal escape of protein cargos

The use of cell-penetrating peptides (CPPs) as biomolecular delivery vehicles holds great promise for therapeutic and other applications, but development has been stymied by poor delivery and lack of endosomal escape. We have developed a CPP-adaptor system capable of efficient intracellular delivery...

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Veröffentlicht in:Journal of cell science 2016-03, Vol.129 (5), p.893-897
Hauptverfasser: Salerno, John C, Ngwa, Verra M, Nowak, Scott J, Chrestensen, Carol A, Healey, Allison N, McMurry, Jonathan L
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container_end_page 897
container_issue 5
container_start_page 893
container_title Journal of cell science
container_volume 129
creator Salerno, John C
Ngwa, Verra M
Nowak, Scott J
Chrestensen, Carol A
Healey, Allison N
McMurry, Jonathan L
description The use of cell-penetrating peptides (CPPs) as biomolecular delivery vehicles holds great promise for therapeutic and other applications, but development has been stymied by poor delivery and lack of endosomal escape. We have developed a CPP-adaptor system capable of efficient intracellular delivery and endosomal escape of user-defined protein cargos. The cell-penetrating sequence of HIV transactivator of transcription was fused to calmodulin, which binds with subnanomolar affinity to proteins containing a calmodulin binding site. Our strategy has tremendous advantage over prior CPP technologies because it utilizes high-affinity non-covalent, but reversible coupling between CPP and cargo. Three different cargo proteins fused to a calmodulin binding sequence were delivered to the cytoplasm of eukaryotic cells and released, demonstrating the feasibility of numerous applications in living cells including alteration of signaling pathways and gene expression.
doi_str_mv 10.1242/jcs.182113
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source MEDLINE; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection; Company of Biologists
subjects Calmodulin - chemistry
Cell-Penetrating Peptides - chemistry
Cell-Penetrating Peptides - metabolism
Endosomes - metabolism
Gene Products, tat - chemistry
HEK293 Cells
Humans
Myoglobin - metabolism
Protein Transport
Recombinant Fusion Proteins - chemistry
Recombinant Fusion Proteins - metabolism
Short Report
title Novel cell-penetrating peptide-adaptors effect intracellular delivery and endosomal escape of protein cargos
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