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Toxicon. 2010 Nov;56(6):990-8. doi: 10.1016/j.toxicon.2010.07.003. Epub 2010 Jul 14.

Camelid single domain antibodies (VHHs) as neuronal cell intrabody binding agents and inhibitors of Clostridium botulinum neurotoxin (BoNT) proteases.

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1
Tufts Cummings School of Veterinary Medicine, Department of Biomedical Sciences, 200 Westboro Road, North Grafton, MA 01536, USA.

Abstract

Botulinum neurotoxins (BoNTs) function by delivering a protease to neuronal cells that cleave SNARE proteins and inactivate neurotransmitter exocytosis. Small (14 kDa) binding domains specific for the protease of BoNT serotypes A or B were selected from libraries of heavy chain only antibody domains (VHHs or nanobodies) cloned from immunized alpacas. Several VHHs bind the BoNT proteases with high affinity (K(D) near 1 nM) and include potent inhibitors of BoNT/A protease activity (K(i) near 1 nM). The VHHs retain their binding specificity and inhibitory functions when expressed within mammalian neuronal cells as intrabodies. A VHH inhibitor of BoNT/A protease was able to protect neuronal cell SNAP25 protein from cleavage following intoxication with BoNT/A holotoxin. These results demonstrate that VHH domains have potential as components of therapeutic agents for reversal of botulism intoxication.

PMID:
20637220
PMCID:
PMC2946066
DOI:
10.1016/j.toxicon.2010.07.003
[Indexed for MEDLINE]
Free PMC Article

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