Engineering TGF-beta superfamily ligands for clinical applications

摘要

TGF-beta superfamily ligands govern normal tissue development and homeostasis, and their dysfunction is a hallmark of many diseases. These ligands are also well defined both structurally and functionally. This review focuses on TGF-beta superfamily ligand engineering for therapeutic purposes, in particular for regenerative medicine and musculoskeletal disorders. We describe the key discovery that structure-guided mutation of receptor-binding epitopes, especially swapping of these epitopes between ligands, results in new ligands with unique functional properties that can be harnessed clinically. Given the promising results with prototypical engineered TGF-beta superfamily ligands, and the vast number of such molecules that remain to be produced and tested, this strategy is likely to hold great promise for the development of new biologics.