Literature DB >> 17660298

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

Yue-Jin Huang1, Yue Huang, Hernan Baldassarre, Bin Wang, Anthoula Lazaris, Martin Leduc, Annie S Bilodeau, Annie Bellemare, Mélanie Côté, Peter Herskovits, Madjid Touati, Carl Turcotte, Loredana Valeanu, Nicolas Lemée, Harvey Wilgus, Isabelle Bégin, Bhim Bhatia, Khalid Rao, Nathalie Neveu, Eric Brochu, Janice Pierson, Duncan K Hockley, Douglas M Cerasoli, David E Lenz, Costas N Karatzas, Solomon Langermann.   

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.

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Year:  2007        PMID: 17660298      PMCID: PMC1934339          DOI: 10.1073/pnas.0702756104

Source DB:  PubMed          Journal:  Proc Natl Acad Sci U S A        ISSN: 0027-8424            Impact factor:   11.205


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