A novel, porcinated human Butyrylcholinesterase catalytically degrades the chemical warfare nerve agent, sarin

Chemical warfare nerve agents (CWNAs) present a global threat to both military and civilian populations.  The acute toxicity of CWNAs stems from their ability to effectively inhibit acetylcholinesterase (AChE).  This inhibition can lead to uncontrolled cholinergic cellular signaling, resulting in cholinergic crisis and, ultimately, death.  While the current FDA-approved standard of care is moderately effective when administered early, development of novel treatment strategies is necessary.  Butyrylcholinesterase (BChE) is an enzyme which displays a high degree of structural homology to AChE.  Unlike AChE, the roles of BChE are uncertain and possibilities are still being explored. However, BChE appears to primarily serve as a bioscavenger of toxic esters due to its ability to accommodate a wide variety of substrates within its active site.  Like AChE, BChE is also readily inhibited by CWNAs. Due to its high affinity for binding CWNAs, and that null-BChE yields no apparent health effects,...