Therapeutic Depletion of Pathogenic Autoantibodies Using Bifunctional Molecules
Date of Award
Fall 2022
Document Type
Dissertation
Degree Name
Doctor of Philosophy (PhD)
Department
Chemistry
First Advisor
Spiegel, David
Abstract
Autoantibodies are the causative agent in several autoimmune conditions. Clinicalstudies have shown that specific removal of autoantibodies through immunoadsorption is therapeutic to patients, but this process is cumbersome, expensive, and comes with health risks of its own. To address this unmet medical need, we have developed bifunctional molecules capable of targeted in vivo depletion of specific autoantibodies, while leaving the healthy antibody repertoire intact. These molecules function through binding of asialoglycoprotein receptor (ASGPR) on the liver on one end, and the target antibodies on the other. Formation of a ternary complex between the three causes endocytosis and degradation of these antibodies. We have shown this approach to be efficacious in treating autoimmune-mediated disease.
Recommended Citation
deRamon, Edward, "Therapeutic Depletion of Pathogenic Autoantibodies Using Bifunctional Molecules" (2022). Yale Graduate School of Arts and Sciences Dissertations. 918.
https://elischolar.library.yale.edu/gsas_dissertations/918
