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Development and Differentiation in Monobodies Based on the Fibronectin Type 3 Domain

Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton 3800, Australia
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Cells 2020, 9(3), 610; https://doi.org/10.3390/cells9030610
Received: 20 December 2019 / Revised: 24 February 2020 / Accepted: 1 March 2020 / Published: 4 March 2020
(This article belongs to the Special Issue Fibronectin in Health and Diseases)
As a non-antibody scaffold, monobodies based on the fibronectin type III (FN3) domain overcome antibody size and complexity while maintaining analogous binding loops. However, antibodies and their derivatives remain the gold standard for the design of new therapeutics. In response, clinical-stage therapeutic proteins based on the FN3 domain are beginning to use native fibronectin function as a point of differentiation. The small and simple structure of monomeric monobodies confers increased tissue distribution and reduced half-life, whilst the absence of disulphide bonds improves stability in cytosolic environments. Where multi-specificity is challenging with an antibody format that is prone to mis-pairing between chains, multiple FN3 domains in the fibronectin assembly already interact with a large number of molecules. As such, multiple monobodies engineered for interaction with therapeutic targets are being combined in a similar beads-on-a-string assembly which improves both efficacy and pharmacokinetics. Furthermore, full length fibronectin is able to fold into multiple conformations as part of its natural function and a greater understanding of how mechanical forces allow for the transition between states will lead to advanced applications that truly differentiate the FN3 domain as a therapeutic scaffold. View Full-Text
Keywords: adnectin; biosensor; fibronectin; monobody; non-antibody scaffold; therapeutic adnectin; biosensor; fibronectin; monobody; non-antibody scaffold; therapeutic
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MDPI and ACS Style

Chandler, P.G.; Buckle, A.M. Development and Differentiation in Monobodies Based on the Fibronectin Type 3 Domain. Cells 2020, 9, 610. https://doi.org/10.3390/cells9030610

AMA Style

Chandler PG, Buckle AM. Development and Differentiation in Monobodies Based on the Fibronectin Type 3 Domain. Cells. 2020; 9(3):610. https://doi.org/10.3390/cells9030610

Chicago/Turabian Style

Chandler, Peter G., and Ashley M. Buckle. 2020. "Development and Differentiation in Monobodies Based on the Fibronectin Type 3 Domain" Cells 9, no. 3: 610. https://doi.org/10.3390/cells9030610

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