Multivalent Antibody Ligands for Clearance of Pathogens

描述（由申请人提供）： 该项目的目标是设计，合成和测试多价配体的要求，以同时结合红细胞和血源性病原体，并通过将其引导到肝脏来清除循环中的病原体。配体将由用抗体片段（Fab '）官能化的开环易位聚合（ROMP）衍生的嵌段共聚物组成。聚合物的一半将含有靶向红细胞表面上的补体受体1型（CR1）受体的Fab'，而另一半将用抗金黄色葡萄球菌的Fab'官能化。该项目是基于这样的知识，即对CR1和其他细胞上的表面抗原都具有特异性的随机交联抗体复合物能够聚集两种细胞类型，并在肝脏中破坏非红细胞。所提出的多价配体通过使用结构均一性提供了对以前类似目标的尝试的显著改进。如果成功的话，这个项目的结果将是一个强大的方法，用于快速和普遍的病原体从循环中去除。

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.