Single domain antibodies as blood–brain barrier delivery vectors

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DOIResolve DOI: http://doi.org/10.1016/j.ics.2005.02.024
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TypeArticle
Proceedings titleInternational Congress Series
ConferenceEsteve Foundation Symposium
ISSN0531-5131
Volume1277
Pages212223; # of pages: 12
SubjectSingle domain antibody; Blood–brain barrier; Drug delivery; Drug targeting; Brain vessels
AbstractAntibodies 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.
Publication date
LanguageEnglish
AffiliationNRC Institute for Biological Sciences; National Research Council Canada
Peer reviewedYes
NPARC number21275324
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Record identifier99ceb37f-5ced-4cc0-bc16-10421cc8a48d
Record created2015-06-09
Record modified2016-05-09
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