IPSEN Innovation, 91940 Les Ulis, France.
I-STEM, INSERM UMR861, Université Evry-Paris Saclay, 91100 Corbeil-Essonne, France.
Int J Mol Sci. 2021 Jul 14;22(14):7524. doi: 10.3390/ijms22147524.
Botulinum neurotoxins (BoNTs) are produced by Clostridium botulinum and are responsible for botulism, a fatal disorder of the nervous system mostly induced by food poisoning. Despite being one of the most potent families of poisonous substances, BoNTs are used for both aesthetic and therapeutic indications from cosmetic reduction of wrinkles to treatment of movement disorders. The increasing understanding of the biology of BoNTs and the availability of distinct toxin serotypes and subtypes offer the prospect of expanding the range of indications for these toxins. Engineering of BoNTs is considered to provide a new avenue for improving safety and clinical benefit from these neurotoxins. Robust, high-throughput, and cost-effective assays for BoNTs activity, yet highly relevant to the human physiology, have become indispensable for a successful translation of engineered BoNTs to the clinic. This review presents an emerging family of cell-based assays that take advantage of newly developed human pluripotent stem cells and neuronal function analyses technologies.
肉毒杆菌神经毒素（BoNTs）由肉毒梭菌产生，是导致肉毒中毒的罪魁祸首，肉毒中毒是一种致命的神经系统疾病，主要由食物中毒引起。尽管 BoNTs 是最有效的有毒物质家族之一，但它们已被广泛应用于美容（减少皱纹）和治疗运动障碍等多个领域。对 BoNTs 生物学的深入了解，以及不同毒素血清型和亚型的可用性，为这些毒素的应用范围的扩大提供了前景。BoNTs 的工程改造被认为是提高这些神经毒素安全性和临床获益的新途径。针对 BoNTs 活性的强大、高通量且具有成本效益的检测方法，与人类生理学高度相关，对于成功地将工程改造后的 BoNTs 转化为临床应用是必不可少的。本文综述了一类新兴的基于细胞的检测方法，这些方法利用了新开发的人类多能干细胞和神经元功能分析技术。
