Organophosphate (OP) toxicants remain an active threat to public health and to warfighters in the military. Current countermeasures require near immediate administration following OP exposure and are reported to have controversial efficacies. Acetylcholinesterase (AChE) fused to the human immunoglobulin 1 (IgG1) Fc domain (AChE‐Fc) is a potential bioscavenger for OP toxicants, but a reproducible AChE‐Fc biomanufacturing strategy remains elusive. This report is the first to establish a comprehensive laboratory‐scale bioprocessing strategy that can reproducibly produce AChE‐Fc and AChE(W86A)‐Fc which is a mutated AChE protein with reduced enzymatic activity. Characterization studies revealed that AChE‐Fc and AChE(W86A)‐Fc are N‐glycosylated dimeric fusion glycoproteins but only AChE‐Fc had the capability to bind to paraoxon (a model OP). This AChE‐Fc fusion glycoprotein bioprocessing strategy can be leveraged during industrial biomanufacturing development, while the research‐grade AChE‐Fc proteins can be used to determine the potential clinical relevance of the countermeasure against OP toxicants.

中文翻译：

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用于制造有机磷毒物生物清除对策的模型乙酰胆碱酯酶-Fc融合糖蛋白生物技术系统

有机磷 (OP) 毒物仍然对公众健康和军队战士构成积极威胁。目前的对策要求在接触 OP 后立即给药，据报道其疗效存在争议。与人免疫球蛋白 1 (IgG1) Fc 结构域融合的乙酰胆碱酯酶 (AChE) (AChE-Fc) 是 OP 毒物的潜在生物清除剂，但可重复的 AChE-Fc 生物制造策略仍然难以实现。该报告首次建立了全面的实验室规模生物加工策略，可以重复生产AChE-Fc和AChE(W86A)-Fc，AChE(W86A)-Fc是一种酶活性降低的突变AChE蛋白。表征研究表明 AChE-Fc 和 AChE(W86A)-Fc 是氮‐糖基化二聚体融合糖蛋白，但只有 AChE-Fc 具有与对氧磷（OP 模型）结合的能力。这种 AChE-Fc 融合糖蛋白生物加工策略可在工业生物制造开发过程中利用，而研究级 AChE-Fc 蛋白可用于确定针对 OP 毒物对策的潜在临床相关性。