Salmonella-based platform for efficient delivery of functional binding proteins to the cytosol.
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Embargo End Date
ICR Authors
Authors
Chabloz, A
Schaefer, JV
Kozieradzki, I
Cronin, SJF
Strebinger, D
Macaluso, F
Wald, J
Rabbitts, TH
Plückthun, A
Marlovits, TC
Penninger, JM
Schaefer, JV
Kozieradzki, I
Cronin, SJF
Strebinger, D
Macaluso, F
Wald, J
Rabbitts, TH
Plückthun, A
Marlovits, TC
Penninger, JM
Document Type
Journal Article
Date
2020-07-03
Date Accepted
2020-06-11
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.
Citation
Communications biology, 2020, 3 (1), pp. 342 - ?
Source Title
Publisher
NATURE PORTFOLIO
ISSN
2399-3642
eISSN
2399-3642
Collections
Research Team
Chromosomal Translocations and Intracellular Antibody Therapeutics