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

Ilyushin DG1, Smirnov IV, Belogurov AA Jr, Dyachenko IA, Zharmukhamedova TIu, Novozhilova TI, Bychikhin EA, Serebryakova MV, Kharybin ON, Murashev AN, Anikienko KA, Nikolaev EN, Ponomarenko NA, Genkin DD, Blackburn GM, Masson P, Gabibov AG
Source: Proc Natl Acad Sci USA
Publication Date: (2013)
Issue: 110(4): 1243–1248
Research Area:
Cells used in publication:
Species: hamster
Tissue Origin: ovarian
Culture Media:
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.