DELIVERY OF ANTI-INFLAMMATORY PROTEINS ACROSS THE HUMAN BLOOD BRAIN BARRIER FOR THE TREATMENT OF TRAUMATIC BRAIN INJURY AND RELATED PATHOLOGIES
- Author(s): Nguyen, Loan Thi Cam
- Advisor(s): LiWang, Patricia
- et al.
Traumatic Brain Injury (TBI) is an injury that occurs following sudden head trauma and results in extensive damage to brain tissue primarily due to the acute inflammatory response. However, current treatment options for TBI are limited due to the difficulty in delivering therapeutic agents to the brain. The severity and consequences of pathologies directly and indirectly associated with TBI have attracted significant medical attention and have stimulated research directed at finding new therapeutic options for the treatment of the inflammation that accompanies TBI. Many studies have identified the crucial role of chemokines and chemokine receptors in triggering and perpetuating this inflammatory response. This study reports a potent drug target for combatting TBI induced inflammation, which is constructed by conjugating the chemokine antagonist, vMIP-II and single chain variable fragment, scFv8D3, of the antibody that selectively binds to Transferrin receptors expressed on external side of the human blood brain barrier (BBB). Combining the functionality of these well-studied anti-inflammatory and transport-oriented proteins would greatly facilitate the delivery of therapeutic agents to the brain. The chimeric protein vMIP-II-L-scFv was successfully designed, expressed in an E. Coli system and refolded using stepwise dialysis with different concentration of Gnd-HCl, Arginine-HCl, and oxidizing agent GSSG, providing a solid platform for the investigation of its BBB transport and anti-inflammatory properties in future studies.