从鼠胚胎干细胞中诱导分化的神经元中对肉毒神经毒素的灵敏和定量检测
Sensitive and quantitative detection of botulinum neurotoxin in neurons derived from mouse embryonic stem cells.
机构信息
Department of Bacteriology, University of Wisconsin-Madison, Madison, WI 53706, USA.
出版信息
Biochem Biophys Res Commun. 2011 Jan 7;404(1):388-92. doi: 10.1016/j.bbrc.2010.11.128. Epub 2010 Dec 3.
Abstract
Botulinum neurotoxins (BoNTs), the most poisonous protein toxins known, represent a serious bioterrorism threat but are also used as a unique and important bio-pharmaceutical to treat an increasing myriad of neurological disorders. The only currently accepted detection method by the United States Food and Drug Administration for biological activity of BoNTs and for potency determination of pharmaceutical preparations is the mouse bioassay (MBA). Recent advances have indicated that cell-based assays using primary neuronal cells can provide an equally sensitive and robust detection platform as the MBA to reliably and quantitatively detect biologically active BoNTs. This study reports for the first time a BoNT detection assay using mouse embryonic stem cells to produce a neuronal cell culture. The data presented indicate that this assay can reliably detect BoNT/A with a similar sensitivity as the MBA.
摘要
肉毒神经毒素（BoNTs）是已知最毒的蛋白质毒素，它们不仅代表着严重的生物恐怖主义威胁，也被用作一种独特而重要的生物制药，用于治疗日益增多的各种神经疾病。美国食品和药物管理局目前唯一认可的 BoNTs 生物活性检测方法和药物制剂效价测定方法是小鼠生物测定法（MBA）。最近的进展表明，使用原代神经元细胞的基于细胞的测定法可以为 MBA 提供同样敏感和强大的检测平台，从而可靠且定量地检测具有生物活性的 BoNTs。本研究首次报道了使用小鼠胚胎干细胞产生神经元细胞培养物的 BoNT 检测测定法。所呈现的数据表明，该测定法可以可靠地检测 BoNT/A，其灵敏度与 MBA 相似。
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