Multivalent Antibody Ligands for Clearance of Pathogens

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DESCRIPTION (provided by applicant): The goal of this project is to design, synthesize, and test the requirements for a multivalent ligand to bind simultaneously to erythrocytes and blood borne pathogens and clear the latter from circulation by directing them to the liver. The ligand will be comprised of a ring opening metathesis polymerization (ROMP)-derived block copolymer functionalized with antibody fragments (Fab'). Half of the polymer will contain Fab' targeted against complement receptor type 1 (CR1) receptors on the surface of erythrocytes, while the other half will be functionalized with Fab' against Staphylococcus aureus. This project is based on the knowledge that randomly cross-linked antibody complexes specific for both CR1 and surface antigens on other cells are able to aggregate the two cell types and deliver the nonerythrocyte to be destroyed in the liver. The multivalent ligand proposed offers significant improvement over previous attempts towards similar goals through the use of structural homogeneity. If successful, the result of this project will be a powerful method for the rapid and general removal of pathogens from circulation.