Adeno-associated virus-mediated expression of human butyrylcholinesterase to treat organophosphate poisoning
Autoři:
Vibhor Gupta aff001; C. Linn Cadieux aff002; Deirdre McMenamin aff001; C. Angelica Medina-Jaszek aff001; Muhammad Arif aff001; Omua Ahonkhai aff001; Erik Wielechowski aff001; Maryam Taheri aff001; Yan Che aff001; Tamara Goode aff001; Maria P. Limberis aff001; Mingyao Li aff001; Douglas M. Cerasoli aff002; Anna P. Tretiakova aff001; James M. Wilson aff001
Působiště autorů:
Gene Therapy Program, Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
aff001; United States Army Medical Research Institute of Chemical Defense, Maryland, United States of America
aff002; Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America
aff003
Vyšlo v časopise:
PLoS ONE 14(11)
Kategorie:
Research Article
doi:
https://doi.org/10.1371/journal.pone.0225188
Souhrn
Rare diseases defined by genetic mutations are classic targets for gene therapy. More recently, researchers expanded the use of gene therapy in non-clinical studies to infectious diseases through the delivery of vectorized antibodies to well-defined antigens. Here, we further extend the utility of gene therapy beyond the “accepted” indications to include organophosphate poisoning. There are no approved preventives for the multi-organ damage resulting from acute or chronic exposure to organophosphates. We show that a single intramuscular injection of adeno-associated virus vector produces peak expression (~0.5 mg/ml) of active human butyrylcholinesterase (hBChE) in mice serum within 3–4 weeks post-treatment. This expression is sustained for up to 140 days post-injection with no silencing. Sustained expression of hBChE provided dose-dependent protection against VX in male and female mice despite detectable antibodies to hBChE in some mice, thereby demonstrating that expression of hBChE in vivo in mouse muscle is an effective prophylactic against organophosphate poisoning.
Klíčová slova:
Antibodies – Blood plasma – Muscle proteins – Organophosphates – Poisoning – Prophylaxis – Gene therapy – Viral vectors
Zdroje
1. John H, van der Schans MJ, Koller M, Spruit HET, Worek F, Thiermann H, et al. Fatal sarin poisoning in Syria 2013: forensic verification within an international laboratory network. Forensic Toxicol. 2018;36(1):61–71. doi: 10.1007/s11419-017-0376-7 29367863
2. Solberg Y, Nachtomi-Shick O, Shemer Y, Alcalay M. [Terror in Japan: mass-intoxication with the nerve-agent sarin]. Harefuah. 1998;135(7–8):268–71, 336, 5. 9885671.
3. Naughton SX, Terry AV Jr. Neurotoxicity in acute and repeated organophosphate exposure. Toxicology. 2018;408:101–12. Epub 2018/08/26. doi: 10.1016/j.tox.2018.08.011 30144465.
4. Colovic MB, Krstic DZ, Lazarevic-Pasti TD, Bondzic AM, Vasic VM. Acetylcholinesterase inhibitors: pharmacology and toxicology. Curr Neuropharmacol. 2013;11(3):315–35. doi: 10.2174/1570159X11311030006 24179466
5. Nachon F, Brazzolotto X, Trovaslet M, Masson P. Progress in the development of enzyme-based nerve agent bioscavengers. Chem Biol Interact. 2013;206(3):536–44. doi: 10.1016/j.cbi.2013.06.012 23811386.
6. Lenz DE, Yeung D, Smith JR, Sweeney RE, Lumley LA, Cerasoli DM. Stoichiometric and catalytic scavengers as protection against nerve agent toxicity: a mini review. Toxicology. 2007;233(1–3):31–9. doi: 10.1016/j.tox.2006.11.066 17188793.
7. Nachon F, Nicolet Y, Viguie N, Masson P, Fontecilla-Camps JC, Lockridge O. Engineering of a monomeric and low-glycosylated form of human butyrylcholinesterase: expression, purification, characterization and crystallization. Eur J Biochem. 2002;269(2):630–7. doi: 10.1046/j.0014-2956.2001.02692.x 11856322.
8. Huang YJ, Huang Y, Baldassarre H, Wang B, Lazaris A, Leduc M, et al. Recombinant human butyrylcholinesterase from milk of transgenic animals to protect against organophosphate poisoning. Proc Natl Acad Sci U S A. 2007;104(34):13603–8. doi: 10.1073/pnas.0702756104 17660298
9. Geyer BC, Kannan L, Garnaud PE, Broomfield CA, Cadieux CL, Cherni I, et al. Plant-derived human butyrylcholinesterase, but not an organophosphorous-compound hydrolyzing variant thereof, protects rodents against nerve agents. Proc Natl Acad Sci U S A. 2010;107(47):20251–6. doi: 10.1073/pnas.1009021107 21059932
10. Bird SB, Dawson A, Ollis D. Enzymes and bioscavengers for prophylaxis and treatment of organophosphate poisoning. Front Biosci (Schol Ed). 2010;2:209–20. doi: 10.2741/s58 20036941.
11. Parikh K, Duysen EG, Snow B, Jensen NS, Manne V, Lockridge O, et al. Gene-delivered butyrylcholinesterase is prophylactic against the toxicity of chemical warfare nerve agents and organophosphorus compounds. J Pharmacol Exp Ther. 2011;337(1):92–101. doi: 10.1124/jpet.110.175646 21205915.
12. Chilukuri N, Duysen EG, Parikh K, diTargiani R, Doctor BP, Lockridge O, et al. Adenovirus-transduced human butyrylcholinesterase in mouse blood functions as a bioscavenger of chemical warfare nerve agents. Mol Pharmacol. 2009;76(3):612–7. doi: 10.1124/mol.109.055665 19542320.
13. Chilukuri N, Duysen EG, Parikh K, Sun W, Doctor BP, Lockridge O, et al. Adenovirus-mediated gene transfer of human butyrylcholinesterase results in persistent high-level transgene expression in vivo. Chem Biol Interact. 2008;175(1–3):327–31. doi: 10.1016/j.cbi.2008.04.009 18499092.
14. Salmon F, Grosios K, Petry H. Safety profile of recombinant adeno-associated viral vectors: focus on alipogene tiparvovec (Glybera(R)). Expert Rev Clin Pharmacol. 2014;7(1):53–65. Epub 2013/12/07. doi: 10.1586/17512433.2014.852065 24308784.
15. Li H, Schopfer LM, Masson P, Lockridge O. Lamellipodin proline rich peptides associated with native plasma butyrylcholinesterase tetramers. Biochem J. 2008;411(2):425–32. doi: 10.1042/BJ20071551 18076380.
16. Peng H, Schopfer LM, Lockridge O. Origin of polyproline-rich peptides in human butyrylcholinesterase tetramers. Chem Biol Interact. 2016;259(Pt B):63–9. doi: 10.1016/j.cbi.2016.02.007 26876904.
17. Murthy V, Gao Y, Geng L, LeBrasseur NK, White TA, Parks RJ, et al. Physiologic and metabolic safety of butyrylcholinesterase gene therapy in mice. Vaccine. 2014;32(33):4155–62. Epub 2014/06/04. doi: 10.1016/j.vaccine.2014.05.067 24892251
18. https://www.proteinatlas.org/ENSG00000114200-BCHE/cell.
19. Gao G, Lu Y, Calcedo R, Grant RL, Bell P, Wang L, et al. Biology of AAV serotype vectors in liver-directed gene transfer to nonhuman primates. Mol Ther. 2006;13(1):77–87. doi: 10.1016/j.ymthe.2005.08.017 16219492.
20. Ellman GL, Courtney KD, Andres V Jr., Feather-Stone RM. A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol. 1961;7:88–95. doi: 10.1016/0006-2952(61)90145-9 13726518.
21. Karnovsky MJ, Roots L. A "Direct-Coloring" Thiocholine Method for Cholinesterases. J Histochem Cytochem. 1964;12:219–21. doi: 10.1177/12.3.219 14187330.
22. Gupta RC, editor. Handbook of Toxicology of Chemical Warfare Agents: Academic Press; 2009.
23. Onder S, Tacal O, Lockridge O. Delipidation of Plasma Has Minimal Effects on Human Butyrylcholinesterase. Frontiers in Pharmacology. 2018;9(117). doi: 10.3389/fphar.2018.00117 29497381
24. Han SO, Ronzitti G, Arnson B, Leborgne C, Li S, Mingozzi F, et al. Erratum: Low-Dose Liver-Targeted Gene Therapy for Pompe Disease Enhances Therapeutic Efficacy of ERT via Immune Tolerance Induction. Mol Ther Methods Clin Dev. 2019;13:431. Epub 2019/05/11. doi: 10.1016/j.omtm.2019.04.005 31073535
25. Han SO, Ronzitti G, Arnson B, Leborgne C, Li S, Mingozzi F, et al. Low-Dose Liver-Targeted Gene Therapy for Pompe Disease Enhances Therapeutic Efficacy of ERT via Immune Tolerance Induction. Mol Ther Methods Clin Dev. 2017;4:126–36. Epub 2017/03/28. doi: 10.1016/j.omtm.2016.12.010 28344998
26. Sun B, Bird A, Young SP, Kishnani PS, Chen YT, Koeberl DD. Enhanced response to enzyme replacement therapy in Pompe disease after the induction of immune tolerance. Am J Hum Genet. 2007;81(5):1042–9. Epub 2007/10/10. doi: 10.1086/522236 17924344
27. Hrabovska A, Bernard V, Krejci E. A novel system for the efficient generation of antibodies following immunization of unique knockout mouse strains. PLoS One. 2010;5(9):e12892. Epub 2010/10/05. doi: 10.1371/journal.pone.0012892 20886120
28. Li B, Duysen EG, Carlson M, Lockridge O. The butyrylcholinesterase knockout mouse as a model for human butyrylcholinesterase deficiency. J Pharmacol Exp Ther. 2008;324(3):1146–54. doi: 10.1124/jpet.107.133330 18056867.
29. Dunn EN, Ferrara-Bowens TM, Chachich ME, Honnold CL, Rothwell CC, Hoard-Fruchey HM, et al. Evaluating mice lacking serum carboxylesterase as a behavioral model for nerve agent intoxication. Toxicol Mech Methods. 2018;28(8):563–72. doi: 10.1080/15376516.2018.1476637 29768075.
30. Greig JA, Calcedo R, Grant RL, Peng H, Medina-Jaszek CA, Ahonkhai O, et al. Intramuscular administration of AAV overcomes pre-existing neutralizing antibodies in rhesus macaques. Vaccine. 2016;34(50):6323–9. Epub 2016/11/08. doi: 10.1016/j.vaccine.2016.10.053 27817961.
31. Greig JA, Peng H, Ohlstein J, Medina-Jaszek CA, Ahonkhai O, Mentzinger A, et al. Intramuscular injection of AAV8 in mice and macaques is associated with substantial hepatic targeting and transgene expression. PLoS One. 2014;9(11):e112268. Epub 2014/11/14. doi: 10.1371/journal.pone.0112268 25393537
32. Lockridge O, Norgren RB Jr., Johnson RC, Blake TA. Naturally Occurring Genetic Variants of Human Acetylcholinesterase and Butyrylcholinesterase and Their Potential Impact on the Risk of Toxicity from Cholinesterase Inhibitors. Chem Res Toxicol. 2016;29(9):1381–92. doi: 10.1021/acs.chemrestox.6b00228 27551784
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PLOS One
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