Protein Superglues to control cells and protect from outbreak threats

Abstract: Many properties of antibodies and other binding proteins are limited by dissociation. A special feature of the bacterium Streptococcus pyogenes enables spontaneous locking together of its surface proteins. Our lab re-engineered this system to generate an irreversible peptide-protein interaction (SpyTag/SpyCatcher). This superglue is genetically-encodable and specific in diverse biological environments. We accelerated reactivity to the diffusion limit and generated variants switchable by light, pH or temperature. SpyTag allows rapid reformatting of antibodies with reporters or effector molecules. SpyTag and its related superglue SnoopTag allow programmable synthesis of antibody/nanobody teams for multiplex control of cell signaling. SpyTag also enables simple reformatting of CAR-T cells, virus-like particles for vaccination, or viral vectors. We have developed an independent bacterial superglue called NeissLock for covalent reaction to unmodified human proteins via an anhydride. Applications will be discussed towards cell therapy and for broad protection against long-standing vaccine challenges and emerging pandemic threats.

Host: Lynne Regan