Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning

Dangerous organophosphorus (OP) compounds have been used as insecticides in agriculture and in chemical warfare. Because exposure to OP could create a danger for humans in the future, butyrylcholinesterase (BChE) has been developed for prophylaxis to these chemicals. Because it is impractical to obt...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2007-08, Vol.104 (34), p.13603-13608
Main Authors: Huang, Yue-Jin, Huang, Yue, Baldassarre, Hernan, Wang, Bin, Lazaris, Anthoula, Leduc, Martin, Bilodeau, Annie S, Bellemare, Annie, Côté, Mélanie, Herskovits, Peter, Touati, Madjid, Turcotte, Carl, Valeanu, Loredana, Lemée, Nicolas, Wilgus, Harvey, Bégin, Isabelle, Bhatia, Bhim, Rao, Khalid, Neveu, Nathalie, Brochu, Eric, Pierson, Janice, Hockley, Duncan K, Cerasoli, Douglas M, Lenz, David E, Karatzas, Costas N, Langermann, Solomon
Format: Article
Language:English
Subjects:
Animals
Animals, Genetically Modified
Biological Sciences
biopharmaceuticals
Butyrylcholinesterase - genetics
Butyrylcholinesterase - isolation & purification
Butyrylcholinesterase - metabolism
Butyrylcholinesterase - pharmacokinetics
Carbohydrate Metabolism
Carbohydrates - analysis
chemoprevention
complementary DNA
Dimers
Enzymes
gene expression
Gene Expression Regulation, Enzymologic
genetic transformation
goat milk
Goats
Guinea Pigs
Half lives
Humans
Lactation
Mice
Milk - drug effects
Milk - enzymology
Nerves
neurotoxicity
Organophosphate Poisoning
organophosphorus compounds
organophosphorus nerve agents
Protein Engineering
protein secretion
recombinant butyrylcholinesterase
recombinant proteins
Recombinant Proteins - genetics
Recombinant Proteins - isolation & purification
Recombinant Proteins - metabolism
Recombinant Proteins - pharmacokinetics
Transgenes
Transgenic animals
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Summary:Dangerous organophosphorus (OP) compounds have been used as insecticides in agriculture and in chemical warfare. Because exposure to OP could create a danger for humans in the future, butyrylcholinesterase (BChE) has been developed for prophylaxis to these chemicals. Because it is impractical to obtain sufficient quantities of plasma BChE to treat humans exposed to OP agents, the production of recombinant BChE (rBChE) in milk of transgenic animals was investigated. Transgenic mice and goats were generated with human BChE cDNA under control of the goat β-casein promoter. Milk from transgenic animals contained 0.1-5 g/liter of active rBChE. The plasma half-life of PEGylated, goat-derived, purified rBChE in guinea pigs was 7-fold longer than non-PEGylated dimers. The rBChE from transgenic mice was inhibited by nerve agents at a 1:1 molar ratio. Transgenic goats produced active rBChE in milk sufficient for prophylaxis of humans at risk for exposure to OP agents.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0702756104