Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning.
نویسندگان
چکیده
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.
منابع مشابه
Expression of Recombinant Human Bche in the Milk of Transgenic Mice
Human butyrylcholinesterase (huBChE) has been successfully used as prophylaxis in animal models to prevent intoxication as a result of exposure to Organophosphate (OP) agents. Since large quantities of enzyme would be required for prophylaxis or treatment, we explored the production of recombinant huBChE (rc-huBChE) in the milk of transgenic animals. A DNA expression vector containing the huBCh...
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ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 104 34 شماره
صفحات -
تاریخ انتشار 2007