Generation and characterization of antibodies for blood-brain barrier penetration

Abstract

The blood-brain barrier (BBB) poses a major obstacle to delivering therapeutic macromolecules into the brain. Recent unpublished findings suggest that a large plasma protein could serve as an endogenous transport shuttle across the BBB. In this thesis, monoclonal antibodies recognizing different regions of this protein were generated using phage display technology. Selected antibodies were produced in human IgG1 format, characterized for binding specificity and affinity, and evaluated in vivo for their ability to cross the BBB. The results demonstrate that antibodies binding to the central monomeric fragment of the shuttle protein can successfully reach the brain, supporting the potential of the pathway for brain-targeted therapies.