Salmonella-based platform for efficient delivery of functional binding proteins to the cytosol
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Salmonella-based platform for efficient delivery of functional binding proteins to the cytosol. / Chabloz, Antoine; Schaefer, Jonas V; Kozieradzki, Ivona; Cronin, Shane J F; Strebinger, Daniel; Macaluso, Francesca; Wald, Jiri; Rabbitts, Terence H; Plückthun, Andreas; Marlovits, Thomas C; Penninger, Josef M.
in: COMMUN BIOL, Jahrgang 3, Nr. 1, 03.07.2020, S. 342.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Salmonella-based platform for efficient delivery of functional binding proteins to the cytosol
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 C
AU - Penninger, Josef M
PY - 2020/7/3
Y1 - 2020/7/3
N2 - 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.
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.
U2 - 10.1038/s42003-020-1072-4
DO - 10.1038/s42003-020-1072-4
M3 - SCORING: Journal article
C2 - 32620833
VL - 3
SP - 342
JO - COMMUN BIOL
JF - COMMUN BIOL
SN - 2399-3642
IS - 1
ER -