A Novel Strategy for Etiologic Factor Removal: Drug-Navigated Clearance System (DNCS).

ABSTRACT

Here, we propose a novel therapeutic concept named drug-navigated clearance system (DNCS), in which a "navigator" decreases the concentration of a target etiologic factor in the blood by steering it to an unusual metabolic pathway. The navigator is composed of protein A (ProA) and dextran sulfate (DexS) and it successfully navigated antibodies (ABs), a model etiologic factor of dilated cardiomyopathy, to hepatocytes in vitro in the presence of low-density lipoprotein (LDL). ProA captured the Fc region of the target antibody while the DexS bound to LDL via the well-known electrostatic interaction. The hepatocytes simultaneously took up LDL via the LDL-receptor and internalized the AB/ProA-DexS complex that was bound to LDL. Therefore, this process demonstrates our attempt to navigate the etiologic factor to an alternate target pathway such as the LDL salvage.