Salmonella-based platform for efficient delivery of functional binding proteins to the cytosol.
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Date
2020-07-03ICR Author
Author
Chabloz, A
Schaefer, JV
Kozieradzki, I
Cronin, SJF
Strebinger, D
Macaluso, F
Wald, J
Rabbitts, TH
Plückthun, A
Marlovits, TC
Penninger, JM
Type
Journal Article
Metadata
Show full item recordAbstract
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.
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Research team
Chromosomal Translocations and Intracellular Antibody Therapeutics
Language
eng
Date accepted
2020-06-11
License start date
2020-07-03
Citation
Communications biology, 2020, 3 (1), pp. 342 - ?
Publisher
NATURE PUBLISHING GROUP