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Selection of phage‐displayed llama single‐domain antibodies that transmigrate across human blood‐brain barrier endothelium
Abstract
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.
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Cited by
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“For their use in targeting drugs across the blood–brain barrier (BBB) into the brain, VHHs were selected that transmigrate the human BBB in an in vitro model and accumulate in the brain after intravenous injection into mice (Muruganandam et al. 2002).”
BackgroundApproaches to transport therapeutic drugs across the blood–brain barrier to treat brain diseases
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The therapeutic potential of nanobodies
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Metadata
- Authors
- Muruganandam, A., Tanha, J., Narang, S., & Stanimirovic, D.
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2001-12-28
- Volume
- 16
- Issue
- 2
- Pages
- 1-22
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2149218172
- Cited by
- 260
- References
- 0
- FWCI
- 2.06
- Type
- journal article
- Language
- en
- Open access
- closed
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- Muruganandam, A., Tanha, J., Narang, S., & Stanimirovic, D. (2002). Selection of phage‐displayed llama single‐domain antibodies that transmigrate across human blood‐brain barrier endothelium. The FASEB Journal. https://doi.org/10.1096/fj.01-0343fje
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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