1. Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning.
- Author
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Huang YJ, Huang Y, Baldassarre H, Wang B, Lazaris A, Leduc M, Bilodeau AS, Bellemare A, Côté M, Herskovits P, Touati M, Turcotte C, Valeanu L, Lemée N, Wilgus H, Bégin I, Bhatia B, Rao K, Neveu N, Brochu E, Pierson J, Hockley DK, Cerasoli DM, Lenz DE, Karatzas CN, and Langermann S
- Subjects
- Animals, Animals, Genetically Modified, Butyrylcholinesterase genetics, Butyrylcholinesterase isolation & purification, Butyrylcholinesterase pharmacokinetics, Carbohydrate Metabolism, Carbohydrates analysis, Gene Expression Regulation, Enzymologic, Goats, Guinea Pigs, Humans, Mice, Protein Engineering, Recombinant Proteins genetics, Recombinant Proteins isolation & purification, Recombinant Proteins metabolism, Recombinant Proteins pharmacokinetics, Butyrylcholinesterase metabolism, Milk drug effects, Milk enzymology, Organophosphate Poisoning
- Abstract
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 beta-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.
- Published
- 2007
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