We present a procedure for optimizing the expression of recombinant tetrameric butyrylcholinesterase that enables large-scale production with the yield >30 mg/liter (>90 mg/roller bottle). Intravenous injection of the preparation significantly increased survival and decreased the severity of symptoms of poisoning with paraoxon, an organophosphorus toxin.
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Terekhov SS, Smirnov IV, Shamborant OG, Bobik TV, Ilyushin DG, Murashev AN, Dyachenko IA, Palikov VA, Knorre VD, Belogurov Jr AA, Ponomarenko NA, Kuzina ES, Genkin DD, Masson P, Gabibov AG. Chemical polysialylation and in vivo tetramerization improve pharmacokinetic characteristics of recombinant human butyrylcholinesterase-based bioscavengers. Acta Naturae. 2015;7(4):136-141.
Eddleston M, Buckley NA, Eyer P, Dawson AH. Management of acute organophosphorus pesticide poisoning. Lancet. 2008;371:597-607.
Eddleston M, Eyer P, Worek F, Juszczak E, Alder N, Mohamed F, Senarathna L, Hittarage A, Azher S, Jeganathan K, Jayamanne S, von Meyer L, Dawson AH, Sheriff MH, Buckley NA. Pralidoxime in acute organophosphorus insecticide poisoning — a randomised controlled trial. PLoS Med. 2009;6(6):e1000104.
Geyer BC, Kannan L, Garnaud PE, Broomfield CA, Cadieux CL, Cherni I, Hodgins SM, Kasten SA, Kelley K, Kilbourne J, Oliver ZP, Otto TC, Puffenberger I, Reeves TE, Robbins N 2nd, Woods RR, Soreq H, Lenz DE, Cerasoli DM, Mor TS. Plant-derived human butyrylcholinesterase, but not an organophosphorous-compound hydrolyzing variant thereof, protects rodents against nerve agents. Proc. Natl Acad. Sci. USA. 2010;107(47):20,251-20,256.
Gunnell D, Eddleston M, Phillips MR, Konradsen F. The global distribution of fatal pesticide self-poisoning: systematic review. BMC Public Health. 2007;7:357.
Huang YJ, Huang Y, Baldassarre H, Wang B, Lazaris A, Leduc M, Bilodeau AS, Bellemare A, Cote M, Herskovits P, Touati M, Turcotte C, Valeanu L, Lemee N, Wilgus H, Begin I, Bhatia B, Rao K, Neveu N, Brochu E, Pierson J, Hockley DK, Cerasoli DM, Lenz DE, Karatzas CN, Langermann S. Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning. Proc. Natl Acad. Sci. USA. 2007;104(34):13,603-13,608.
Masson P, Rochu D. Catalytic bioscavengers against toxic esters, an alternative approach for prophylaxis and treatments of poisonings. Acta Naturae. 2009;1(1):68-79.
Mumford H, Docx CJ, Price ME, Green AC, Tattersall JE, Armstrong SJ. Human plasma-derived BuChE as a stoichiometric bioscavenger for treatment of nerve agent poisoning. Chem. Biol. Interact. 2013;203(1):160-166.
Rosenberg YJ, Gearhart J, Mao L, Jiang X, Hernandez-Abanto S. Protection against paraoxon toxicity by an intravenous pretreatment with polyethylene-glycol-conjugated recombinant butyrylcholinesterase in macaques. Chem. Biol. Interact. 2014;210:20-25.
Saxena A, Sun W, Dabisch PA, Hulet SW, Hastings NB, Jakubowski EM, Mioduszewski RJ, Doctor BP. Pretreatment with human serum butyrylcholinesterase alone prevents cardiac abnormalities, seizures, and death in Göttingen minipigs exposed to sarin vapor. Biochem. Pharmacol. 2011;82(12):1984-1993.
Shenouda J, Green P, Sultatos L. An evaluation of the inhibition of human butyrylcholinesterase and acetylcholinesterase by the organophosphate chlorpyrifos oxon. Toxicol. Appl. Pharmacol. 2009;241(2):135-142.
Sun W, Doctor BP, Lenz DE, Saxena A. Long-term effects of human butyrylcholinesterase pretreatment followed by acute soman challenge in cynomolgus monkeys. Chem. Biol. Interact. 2008;175(1-3):428-430.
Terekhov S, Smirnov I, Bobik T, Shamborant O, Zenkova M, Chernolovskaya E, Gladkikh D, Murashev A, Dyachenko I, Palikov V, Palikova Y, Knorre V, Belogurov A Jr, Ponomarenko N, Blackburn GM, Masson P, Gabibov A. A novel expression cassette delivers efficient production of exclusively tetrameric human butyrylcholinesterase with improved pharmacokinetics for protection against organophosphate poisoning. Biochimie. 2015;118:51-59.
Wille T, Thiermann H, Worek F. In vitro kinetics of nerve agent degradation by fresh frozen plasma (FFP). Arch. Toxicol. 2014;88(2) P. 301-307.
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Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 163, No. 4, pp. 425-430, April, 2016
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Terekhov, S.S., Palikov, V.A., Palikova, Y.A. et al. Application of Tetrameric Recombinant Human Butyrylcholinesterase as a Biopharmaceutical for Amelioration of Symptoms of Acute Organophosphate Poisoning. Bull Exp Biol Med 163, 430–435 (2017). https://doi.org/10.1007/s10517-017-3821-z
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DOI: https://doi.org/10.1007/s10517-017-3821-z