National Research Council of Canada. NRC Institute for Biological Sciences
Esteve Foundation Symposium
single domain antibody; blood–brain barrier; drug delivery; drug targeting; brain vessels
Antibodies against various receptors that undergo transcytosis across brain capillary endothelium including transferrin, insulin growth factor and low-density lipoprotein receptors have been used as vectors to deliver drugs or therapeutic peptides into the brain. In this study, recently discovered llama single domain antibody FC5 that transmigrates across cerebral endothelial cells (CEC) in vitro and blood–brain barrier (BBB) in vivo was engineered to provide ‘linker’ groups for conjugation with large molecules. Horseradish peroxidase (HRP)-tagged IgG was chemically attached to FC5 through an engineered free cysteine (cysFC5) and HRP-IgG-cysFC5 construct was shown to transmigrate across in vitro BBB model. Transmigration of FC5 across CEC was enhanced by pentamerizing FC5. Pentameric FC5 also demonstrated increased binding to microdissected human, mouse and rat brain vessels.
International Congress Series1277 (April 2005): 212–223.