Research on constructions and applications of the engineered antibodies

Abstract

Antibody is Y-shaped glycoprotein composed of several immunoglobulin domains and plays a critical role in humoral immune response to identify and neutralize foreign antigens. The ability of antibody to bind highly specific is useful in various fields, not only therapeutic but also bioengineering. To overcome drawbacks of antibody, researchers developed antibody variants including Fab, Fv and diabody and discovered new antibodies from other species such as camelid. In spite of their efforts, there still have been limitations. We studied to overcome the limitations and improve their advantages. To enhance utility of diabody, we determined 10 crystal structures of diabodies and revealed that diabody had flexible interface between Fv domains and introduction of disulfide bond made the interface rigid. Furthermore, to increase valence over 2 for enhancing functional affinity, we constructed multivalent scaffold and confirmed that increase of valence enhance functional affinity and multivalent scaffold could distinguish between fibril and monomer by ELISA. These engineered antibodies may have broad applications in numerous fields including the construction of protein nano-assemblies, protein crystallization, the single particle analysis of protein cryo-EM, and the diagnosis for amyloid fibril.