TY  - JOUR
AU  - Chabloz, Antoine
AU  - Schaefer, Jonas V.
AU  - Kozieradzki, Ivona
AU  - Cronin, Shane J. F.
AU  - Strebinger, Daniel
AU  - Macaluso, Francesca
AU  - Wald, Jiri
AU  - Rabbitts, Terence H.
AU  - Plückthun, Andreas
AU  - Marlovits, Thomas
AU  - Penninger, Josef M.
TI  - Salmonella-based platform for efficient delivery of functional binding proteins to the cytosol
JO  - Communications biology
VL  - 3
IS  - 1
SN  - 2399-3642
CY  - London
PB  - Springer Nature
M1  - PUBDB-2021-00539
SP  - 342
PY  - 2020
AB  - 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.
KW  - Bacterial Proteins: genetics
KW  - Bacterial Proteins: metabolism
KW  - Carrier Proteins: genetics
KW  - Carrier Proteins: metabolism
KW  - Cytosol: metabolism
KW  - HCT116 Cells
KW  - HeLa Cells
KW  - Humans
KW  - Neoplasm Proteins: genetics
KW  - Neoplasm Proteins: metabolism
KW  - Recombinant Proteins: genetics
KW  - Recombinant Proteins: metabolism
KW  - Salmonella typhimurium: genetics
KW  - Salmonella typhimurium: growth & development
KW  - Salmonella typhimurium: metabolism
KW  - Type III Secretion Systems: genetics
KW  - Type III Secretion Systems: metabolism
KW  - Bacterial Proteins (NLM Chemicals)
KW  - Carrier Proteins (NLM Chemicals)
KW  - Neoplasm Proteins (NLM Chemicals)
KW  - Recombinant Proteins (NLM Chemicals)
KW  - Type III Secretion Systems (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:32620833
UR  - <Go to ISI:>//WOS:000549964800005
DO  - DOI:10.1038/s42003-020-1072-4
UR  - https://bib-pubdb1.desy.de/record/454465
ER  -