Scalable Production of Recombinant Human Butyrylcholinesterase (rBCHE)

Scalable Production of Recombinant Human Butyrylcholinesterase (rBCHE) Scalable Production of Recombinant Human Butyrylcholinesterase (rBCHE) The major goal of the ASU project is to provide KBP with expertise in protein engineering to create a recombinant butyrylcholinesterase (rBChE) that has the same pharmacokinetic profile as a plasma-derived human butyrylcholinesterase (hBChE) butyrylcholinesterase. ASU will provide DNA sequences to KBP that encode enzyme variants to KBP for rBChE production in Nicotiana benthamiana, to allow them to demonstrate scalable, cost-effective biomanufacturing of rBChE that may be used to generate clinical trial lots and ultimately commercial scale production of the enzyme for the sponsor, Defense Advance Resarch Project Agency. Proposed work in is based on extensive experience gained in the Mor laboratory on expressing human cholinesterases in plants (Mor et al., 2001; Mor and Soreq, 2004; Geyer et al., 2005; Evron et al., 2007; Geyer et al., 2007; Geyer et al., 2008; Woods et al., 2008; Geyer et al., 2009; Geyer et al., 2010a; Geyer et al., 2010b). The proposed effort will provide DNA coding sequences and/or vectors containing a plant-optimized genes coding for human BChE or derivatives thereof. The Mor lab will work together with KBP to adapt purification protocols developed in the Mor lab for larger scale and will provide expertise consult for work done at KBP. ASU will screen in vivo a number of preparations of plant-derived BChE variants for a favorable PK profile.