Goldbody: Artificial Antibody That Can Discriminate Homologous Antigens

Many efforts have been devoted to developing various antibody alternatives to overcome the limitations of conventional antibodies. One such alternative is goldbody, an artificial antibody created using a unique goldization technology that involves grafting and restoring the native conformation of the complementarity-determining regions (CDRs) of antibodies onto gold nanoparticles (AuNPs). Goldbodies exhibit the same binding specificity as the original antibodies, but are more stable. However, it has not yet been demonstrated whether goldbodies can discriminate between homologous antigens in the same way as conventional antibodies do. Using hen egg white lysozyme (HEWL) and human lysozyme (hLYZ) as highly homologous antigen models, we demonstrate here that two anti-HEWL goldbodies bind to HEWL with a single-site-based affinity that is one order of magnitude stronger than that for hLYZ. To further demonstrate the high specificity of goldbodies, we developed an anti-hLYZ goldbody that binds to hLYZ with a single-site-based affinity that is one order of magnitude stronger than that for HEWL. These results show that the high specificity of goldbodies is due to the successful restoration of the native conformation of the grafted CDRs on AuNPs, highlighting the potential of the goldization technology to create artificial antibodies as an alternative to conventional antibodies.