A synthetic designer protein AB204 is for bone fracture and spinal fusion (#27)
Transforming Growth Factor-beta (TGF-beta) superfamily ligands deliver messages such as differentiation or any other biological functions. Defective functions of these signaling systems can result in various disorders including cancer, immune disorders, heart and neuronal disorders. We started out with our knowledge of three-dimensional structures of Bone Morphogenetic Proteins (BMPs) to engineer these molecules. Below is one such example that we developed for potential clinical uses in bone disorders.
Among 33 members for this TGF-beta superfamily, BMP-2 is widely in clinical use for bone repairs including spinal fusion. We BMPs are originally found in the bone extract as a molecule to stimulate bone growth. In the case of bone fusion, we have used Activin and BMP-2 to create AB204, a chimeric fusion protein derived from Activin and BMP-2 molecules, based on their three-dimensional structures and their receptor-binding modes. AB204 consists of approximately 100 amino acids, half of which originate from BMP-2 and the other half from Activin (Allendorph et al., 2011). AB204 indeed shows highly effective bone-forming capability (Yoon et al., 2014). It promises to be a very powerful osteogenic inducer. Similar approaches are being pursued with other related molecules to create other synthetic biologics for clinical purposes.