Engineering TGF-B proteins to restore tissue homeostasis

The Transforming Growth Factor-beta (TGF-β) superfamily is a large family of proteins that are master regulators of tissue homeostasis. Their deregulated activities are associated with various human diseases. While numerous therapeutic agents have been developed for reducing supra-physiological levels of these proteins, progress toward therapeutics to restore protein levels has been less successful. This research demonstrates that by making targeted modifications to the amino acid sequences of selected TGF-β ligands, their half-lives, bioactivity, and activation status can be improved. Taken together, these approaches form a blueprint that will aid further research into TGF-β therapeutics.