Organophosphorus agents (OP) are used as pesticides in developing countries. Acute poisoning is common because of insufficient control, poor storage, ready availability, and inadequate education amongst farmers. OPs include nerve agents like Tabun, Sarin, Soman, Cyclosarin, VX, and VR. The creation of effective bioscavengers as a pretreatment for exposure to OPs is a challenging medical objective.
Mike Blackburn, University of Sheffield, UK, and colleagues report a recombinant method using chemical polysialylation to generate bioscavengers stable in the bloodstream. They developed a CHO-based expression system by using gene encoding human butyrylcholinesterase and a proline-rich peptide under elongation factor promoter control. This resulted in self-assembling, active enzyme multimers. Polysialylation gives bioscavengers with enhanced pharmacokinetics.
Mice, which were treated with the new enzyme after being subjected to 63 mg of the VR agent (S-(2-(diethylamino)ethyl) O-isobutyl methanephosphonothioate), enough to kill several of them, all survived.
- Chemical polysialylation of human recombinant butyrylcholinesterase delivers a long-acting bioscavenger for nerve agents in vivo,
Denis G. Ilyushin, Ivan V. Smirnov, Alexey A. Belogurov, Jr., Igor A. Dyachenko, Tatiana Iu. Zharmukhamedova, Tatjana I. Novozhilova, Eugene A. Bychikhin, Marina V. Serebryakova, Oleg N. Kharybin, Arkadii N. Murashev, Konstantin A. Anikienko, Eugene N. Nikolaev, Natalia A. Ponomarenko, Dmitry D. Genkin, G. Michael Blackburn, Patrick Masson, Alexander G. Gabibov,
Proc. Nat. Acad. Sci. 2013.