Creation and Evaluation of a Single-chain Antibody Tetramer that Targets Brain Endothelial Cells.
Creation and Evaluation of a Single-chain Antibody Tetramer that Targets Brain Endothelial Cells.
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DOI：
10.1002/aic.14348
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发表时间：
2014-04-01
期刊：
影响因子：
3.7
通讯作者：
Shusta, Eric V.
中科院分区：
文献类型：
--
作者：
Zhang, Xiaobin;Wang, Xin Xiang;Shusta, Eric V.
Antibodies that target and internalize into blood-brain barrier (BBB) endothelial cells offer promise as drug delivery agents. Previously, we identified a single-chain antibody (scFvA) capable of binding to the BBB. In an attempt to improve the binding and internalization properties of the single chain antibody (scFvA), a biotinylation tag (Avitag) was fused to scFvA and the protein secreted by yeast. The scFvA-Avitag could be biotinylated by yeast-displayed BirA enzyme and biotinylated scFvA-Avitag could be used to create scFv tetramers. Tetramerization of scFvA improved the internalization of scFvA into BBB endothelial cells, and biotinylated scFvA-Avitag could also be used to target streptavidin-coated quantum dots for BBB endothelial cell internalization. Perfusing the rat brain with scFvA-tetramer confirmed that the antigen targeted by scFvA is distributed on blood side of the BBB, suggesting the potential for downstream application of scFvA in brain-targeted drug delivery.
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