Phoolcharoen, W; Prehaud, C; van Dolleweerd, C; Both, L; da Costa, A; Lafon, M; Ma, J
(2017)
Enhanced transport of plant-produced rabies single chain antibody-RVG peptide fusion protein across an in cellulo blood-brain barrier device.
Plant Biotechnology Journal, 15 (10).
pp. 1331-1339.
ISSN 1467-7652
https://doi.org/10.1111/pbi.12719
SGUL Authors: Ma, Julian
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Abstract
The biomedical applications of antibody engineering are developing rapidly and have been expanded to plant expression platforms. In this study, we have generated a novel antibody molecule in planta for targeted delivery across the blood–brain barrier (BBB). Rabies virus (RABV) is a neurotropic virus for which there is no effective treatment after entry into the central nervous system. This study investigated the use of a RABV glycoprotein peptide sequence to assist delivery of a rabies neutralizing single-chain antibody (ScFv) across an in cellulo model of human BBB. The 29 amino acid rabies virus peptide (RVG) recognizes the nicotinic acetylcholine receptor (nAchR) at neuromuscular junctions and the BBB. ScFv and ScFv-RVG fusion proteins were produced in Nicotiana benthamiana by transient expression. Both molecules were successfully expressed and purified, but the ScFv expression level was significantly higher than that of ScFv-RVG fusion. Both ScFv and ScFv-RVG fusion molecules had potent neutralization activity against RABVin cellulo. The ScFv-RVG fusion demonstrated increased binding to nAchR and entry into neuronal cells, compared to ScFv alone. Additionally, a human brain endothelial cell line BBB model was used to demonstrate that plant-produced ScFv-RVGP fusion could translocate across the cells. This study indicates that the plant-produced ScFv-RVGP fusion protein was able to cross the in celluloBBB and neutralize RABV.
Item Type: | Article | ||||||||||||
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Additional Information: | © 2017 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. | ||||||||||||
Keywords: | Biotechnology, 10 Technology, 06 Biological Sciences, 11 Medical And Health Sciences | ||||||||||||
SGUL Research Institute / Research Centre: | Academic Structure > Infection and Immunity Research Institute (INII) | ||||||||||||
Journal or Publication Title: | Plant Biotechnology Journal | ||||||||||||
ISSN: | 1467-7652 | ||||||||||||
Dates: |
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Publisher License: | Creative Commons: Attribution 4.0 | ||||||||||||
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URI: | https://openaccess.sgul.ac.uk/id/eprint/108690 | ||||||||||||
Publisher's version: | https://doi.org/10.1111/pbi.12719 |
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