Generating FN3‐Based Affinity Reagents Through Phage Display

Gorman, Kevin Thomas; McGinnis, Jennifer E.; Kay, Brian K.

doi:10.1002/cpch.39

Cited by 5 publications

(2 citation statements)

References 61 publications

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“…The current field of monobody development also benefits from mature technologies that can deliver binding reagents on demand [37] through yeast surface display [38], phage display [39] and mRNA display [40]. The scaffold is also viable for grafting and evolution from single peptide 'anchors' [18,[41][42][43] or CDR-like loop grafting between FN3 scaffolds [44][45][46].…”

Section: Modern Fn3 Derivatives In Developmentmentioning

confidence: 99%

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

Chandler

Buckle

2020

Cells

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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.

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Section: Modern Fn3 Derivatives In Developmentmentioning

confidence: 99%

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

Chandler

Buckle

2020

Cells

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“…The current field of monobody development benefits from mature technologies that can deliver binding reagents on demand [36] through yeast surface display [37], phage display [38] and mRNA display [39]. The scaffold is also viable for grafting and evolution from single peptide 'anchors' [18,[40][41][42] or CDR-like loop grafting between FN3 scaffolds [43][44][45].…”

Section: Modern Fn3 Derivatives In Developmentmentioning

confidence: 99%

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

Chandler

Buckle

2020

Preprint

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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 design of new therapeutics. In response, clinical 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 of chains, 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.

show abstract