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@ARTICLE{Chabloz:454465,
author = {Chabloz, Antoine and Schaefer, Jonas V. and Kozieradzki,
Ivona and Cronin, Shane J. F. and Strebinger, Daniel and
Macaluso, Francesca and Wald, Jiri and Rabbitts, Terence H.
and Plückthun, Andreas and Marlovits, Thomas and Penninger,
Josef M.},
title = {{S}almonella-based platform for efficient delivery of
functional binding proteins to the cytosol},
journal = {Communications biology},
volume = {3},
number = {1},
issn = {2399-3642},
address = {London},
publisher = {Springer Nature},
reportid = {PUBDB-2021-00539},
pages = {342},
year = {2020},
abstract = {Protein-based affinity reagents (like antibodies or
alternative binding scaffolds) offer wide-ranging
applications for basic research and therapeutic approaches.
However, whereas small chemical molecules efficiently reach
intracellular targets, the delivery of macromolecules into
the cytosol of cells remains a major challenge; thus
cytosolic applications of protein-based reagents are rather
limited. Some pathogenic bacteria have evolved a conserved
type III secretion system (T3SS) which allows the delivery
of effector proteins into eukaryotic cells. Here, we enhance
the T3SS of an avirulent strain of Salmonella typhimurium to
reproducibly deliver multiple classes of recombinant
proteins into eukaryotic cells. The efficacy of the system
is probed with both DARPins and monobodies to functionally
inhibit the paradigmatic and largely undruggable RAS
signaling pathway. Thus, we develop a bacterial secretion
system for potent cytosolic delivery of therapeutic
macromolecules.},
keywords = {Bacterial Proteins: genetics / Bacterial Proteins:
metabolism / Carrier Proteins: genetics / Carrier Proteins:
metabolism / Cytosol: metabolism / HCT116 Cells / HeLa Cells
/ Humans / Neoplasm Proteins: genetics / Neoplasm Proteins:
metabolism / Recombinant Proteins: genetics / Recombinant
Proteins: metabolism / Salmonella typhimurium: genetics /
Salmonella typhimurium: growth $\&$ development / Salmonella
typhimurium: metabolism / Type III Secretion Systems:
genetics / Type III Secretion Systems: metabolism /
Bacterial Proteins (NLM Chemicals) / Carrier Proteins (NLM
Chemicals) / Neoplasm Proteins (NLM Chemicals) / Recombinant
Proteins (NLM Chemicals) / Type III Secretion Systems (NLM
Chemicals)},
cin = {CSSB-UKE},
ddc = {570},
cid = {I:(DE-H253)CSSB-UKE-20141216},
pnm = {6215 - Soft Matter, Health and Life Sciences (POF3-621)},
pid = {G:(DE-HGF)POF3-6215},
experiment = {EXP:(DE-MLZ)NOSPEC-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:32620833},
UT = {WOS:000549964800005},
doi = {10.1038/s42003-020-1072-4},
url = {https://bib-pubdb1.desy.de/record/454465},
}