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 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.
PharmAthene Canada, Inc., 7150 Alexander-Fleming, Montreal, QC, Canada H4S 2C8. yjhuang@pharmathene.ca
Yue-Jin
YJ
Huang
Yue
Y
Huang
Hernan
H
Baldassarre
Bin
B
Wang
Anthoula
A
Lazaris
Martin
M
Leduc
Annie S
AS
Bilodeau
Annie
A
Bellemare
Mélanie
M
Côté
Peter
P
Herskovits
Madjid
M
Touati
Carl
C
Turcotte
Loredana
L
Valeanu
Nicolas
N
Lemée
Harvey
H
Wilgus
Isabelle
I
Bégin
Bhim
B
Bhatia
Khalid
K
Rao
Nathalie
N
Neveu
Eric
E
Brochu
Janice
J
Pierson
Duncan K
DK
Hockley
Douglas M
DM
Cerasoli
David E
DE
Lenz
Costas N
CN
Karatzas
Solomon
S
Langermann
D000818:Animals; D030801:Animals, Genetically Modified; D002091:Butyrylcholinesterase / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism* / Q000493:pharmacokinetics; D050260:Carbohydrate Metabolism; D002241:Carbohydrates / Q000032:analysis; D015971:Gene Expression Regulation, Enzymologic; D006041:Goats; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D008892:Milk / Q000187:drug effects* / Q000201:enzymology*; D062025:Organophosphate Poisoning; D015202:Protein Engineering; D011994:Recombinant Proteins / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism / Q000493:pharmacokinetics
D002241:Carbohydrates; D011994:Recombinant Proteins; D002091:Butyrylcholinesterase