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.
Huang
Yue-Jin
YJ
PharmAthene Canada, Inc., 7150 Alexander-Fleming, Montreal, QC, Canada H4S 2C8. yjhuang@pharmathene.ca
Huang
Yue
Y
Baldassarre
Hernan
H
Wang
Bin
B
Lazaris
Anthoula
A
Leduc
Martin
M
Bilodeau
Annie S
AS
Bellemare
Annie
A
Côté
Mélanie
M
Herskovits
Peter
P
Touati
Madjid
M
Turcotte
Carl
C
Valeanu
Loredana
L
Lemée
Nicolas
N
Wilgus
Harvey
H
Bégin
Isabelle
I
Bhatia
Bhim
B
Rao
Khalid
K
Neveu
Nathalie
N
Brochu
Eric
E
Pierson
Janice
J
Hockley
Duncan K
DK
Cerasoli
Douglas M
DM
Lenz
David E
DE
Karatzas
Costas N
CN
Langermann
Solomon
S
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