Intracellular Protein Delivery System Using a Target-Specific Repebody and Translocation Domain of Bacterial Exotoxin

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With the high efficacy of protein-based therapeutics and plenty of intracellular drug targets, cytosolic protein delivery in a cell-specific manner has attracted considerable attention in the field of precision medicine. Herein, we present an intracellular protein delivery system based on a target-specific repebody and the translocation domain of Pseudomonas aeruginosa exotoxin A. The delivery platform was constructed by genetically fusing an EGFR-specific repebody as a targeting moiety to the translocation domain, while a protein cargo was fused to the C-terminal end of the delivery platform. The delivery platform was revealed to efficiently translocate a protein cargo to the cytosol in a target-specific manner. We demonstrate the utility and potential of the delivery platform by showing a remarkable tumor regression with negligible toxicity in a xenograft mice model when gelonin was used as the cytotoxic protein cargo. The present platform can find wide applications to the cell-selective cytosolic delivery of diverse proteins in many areas.
Publisher
AMER CHEMICAL SOC
Issue Date
2017-11
Language
English
Article Type
Article
Keywords

IN-VITRO; DRUG-DELIVERY; CANCER; TOXIN; VIVO; EGFR; ANTIBODY; THERAPY; GELONIN; DESIGN

Citation

ACS CHEMICAL BIOLOGY, v.12, no.11, pp.2891 - 2897

ISSN
1554-8929
DOI
10.1021/acschembio.7b00562
URI
http://hdl.handle.net/10203/228590
Appears in Collection
BS-Journal Papers(저널논문)
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