Chemical polysialylation of human recombinant butyrylcholinesterase delivers a long-acting bioscavenger for nerve agents in vivo.

Ilyushin, Denis G; Smirnov, Ivan V; Belogurov, Alexey A; Dyachenko, Igor A; Zharmukhamedova, Tatiana Iu; Novozhilova, Tatjana I; Bychikhin, Eugene A; Serebryakova, Marina V et al. · Proc Natl Acad Sci U S A · 2013

basic_science · Level V

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Abstract

The creation of effective bioscavengers as a pretreatment for exposure to nerve agents is a challenging medical objective. We report a recombinant method using chemical polysialylation to generate bioscavengers stable in the bloodstream. Development of a CHO-based expression system using genes encoding human butyrylcholinesterase and a proline-rich peptide under elongation factor promoter control resulted in self-assembling, active enzyme multimers. Polysialylation gives bioscavengers with enhanced pharmacokinetics which protect mice against 4.2 LD(50) of S-(2-(diethylamino)ethyl) O-isobutyl methanephosphonothioate without perturbation of long-term behavior.

Medical subject headings