Selection of phage-displayed llama single-domain antibodies that transmigrate across human blood-brain barrier endothelium

被引：189

作者：

Muruganandam, A ^{[1
]}

Tanha, J ^{[1
]}

Narang, S ^{[1
]}

Stanimirovic, D ^{[1
]}

机构：

[1] Natl Res Council Canada, Inst Biol Sci, Ottawa, ON K1A 0R6, Canada

来源：

FASEB JOURNAL | 2001年 / 15卷 / 14期

关键词：

phage display library; brain endothelium; drug delivery;

D O I：

10.1096/fj.01-0343fje

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (similar to 14 kDa) antibodies have characteristics essential for a carrier-vector and can be used to facilitate drug transport across the BBB.

引用

页码：240 / +

页数：22

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