Production of a stable recombinant human butyrylcholinesterase

Human butyrylcholinesterase (BChE) is an effective bioscavenger of organophosphates and has potential for acting as a pre-exposure prophylactic or post-exposure treatment for organophosphate (OP) nerve agents, such as sarin. Ideally, a single dose of BChE could be administered and protect the warfighter for days or even weeks while in combat. To be effective in a military setting, especially as a prophylactic, BChE must have a very long serum half-life and must be non-immunogenic. It is now well-established that the plasma half-life of recombinant BChE is strongly affected by the extent of its oligomerization, glycosylation, and sialylation. During Phase II, we will scale up the expression and purification of a lead candidate recombinant BChE that meets or exceeds the blood serum half-life of wild-type human BChE. Efficacy of the recombinant BChE will be confirmed in vitro and in vivo, and a preliminary regulatory strategy will be established for evaluation by the FDA.