Adenovirus-Transduced Human Butyrylcholinesterase in Mouse Blood Functions as a Bioscavenger of Chemical Warfare Nerve Agents

• DOI: 10.1124/mol.109.055665
• Publication Date: 2009-06-20T01:45:58Z
• Authors: Nageswararao Chil...; Ellen G. Duysen; Kalpana Parikh; Robert diTargiani; Bhupendra P. Doctor; Oksana Lockridge; Ashima Saxena
• Keywords: Butyrylcholinesterase

Human serum butyrylcholinesterase (Hu BChE) is a promising therapeutic against the toxicity of chemical warfare nerve agents. We have showed previously that recombinant (r) Hu BChE can be expressed at very high levels, 400 to 600 U/ml in mouse blood, by delivering gene using adenovirus (Ad). Here, we report biochemical properties Ad-expressed full-length and truncated rHu blood. The molecular sizes subunit its oligomers were similar those native BChE, although only small portion underwent assembly into dimers tetramers. As expected, Ad containing transduced expression monomeric only. Compared with 415 U per milliliter tissues including liver, lung, heart, brain, kidney, muscle, intestine, diaphragm, salivary gland, fat &lt;10 U/g activity. blood neutralized soman <i>O</i>-ethyl <i>S</i>-2-<i>N</i>,<i>N</i>-diisopropylaminoethyl methylphosphonothiolate rates vitro. Because rapidly decreased 6 days after virus administration, sera assayed for presence anti-Hu antibodies. Anti-Hu antibodies detected on day 7 increased amounts thereafter, which coincided loss sera. In conclusion, delivery strategy provide protection multiple lethal doses agents vivo.