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Selection of phage‐displayed llama single‐domain antibodies that transmigrate across human blood‐brain barrier endothelium
Author(s) -
Muruganandam Arumugam,
Tanha Jamshid,
Narang Saran,
Stanimirovic Danica
Publication year - 2002
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.01-0343fje
Subject(s) - phage display , blood–brain barrier , single domain antibody , antibody , biology , microbiology and biotechnology , virology , peptide library , gene , immunology , peptide sequence , genetics , central nervous system , neuroscience
Delivery to the brain of drugs, peptides, and genes depends on the availability of brain‐specific delivery vectors. We used a phage‐displayed library of llama single‐domain antibodies (sdAbs) to enrich for species that selectively bind to and are internalized by human cerebromicrovascular endothelial cells (HCEC). Two sdAbs (FC5 and FC44) were selected, sequenced, subcloned, and expressed as fusion proteins with c‐Myc‐His 5 tags. Similar to phage‐displayed sdAbs, soluble FC5 and FC44 were shown to selectively bind HCEC and to transmigrate across an in vitro human blood‐brain barrier (BBB) model. Both FC5 and FC44, in contrast to an unrelated llama sdAb, were also detected in the brain after i.v. injection into mice. These small (~14 kDa) antibodies have characteristics essential for a carrier‐vector and can be used to facilitate drug transport across the BBB.