PDF(Pubmed)
Abstract：
Among all natural and synthetic toxins, botulinum neurotoxins (BoNTs), produced by Clostridium botulinum in an anaerobic environment, are the most toxic polymer proteins. Currently, the most effective modalities for botulism prevention and treatment are vaccination and antitoxin use, respectively. However, these modalities are associated with long response time for active immunization, side effects, and donor limitations. As such, the development of more promising botulism prevention and treatment modalities is warranted. Here, we designed an mRNA encoding B9-hFc - a heavy-chain antibody fused to VHH and human Fc that can neutralize BoNT serotype B (BoNT/B) effectively - and assessed its expression in vitro and in vivo. The results confirmed that our mRNA demonstrates good expression in vitro and in vivo. Moreover, a single mRNA lipid nanoparticle injection effectively prevents BoNT/B intoxication in vivo, with effects comparable to those of protein antibodies. In conclusion, we explored and clarified whether mRNA drugs encoding neutralizing antibodies prevent BoNT/B intoxication. Our results provide an efficient strategy for further research on the prevention and treatment of intoxication by botulinum toxin.
摘要：
在所有天然和合成毒素中，肉毒杆菌神经毒素（BoNTs），肉毒梭菌在厌氧环境中产生，是毒性最强的聚合物蛋白。目前,预防和治疗肉毒杆菌中毒的最有效方式是接种疫苗和使用抗毒素，分别。然而,这些模式与主动免疫应答时间长有关，副作用,和捐赠者的限制。因此，有必要开发更有前景的肉毒杆菌中毒预防和治疗方式.这里,我们设计了一种编码B9-hFc的mRNA-一种与VHH和人Fc融合的重链抗体，可以有效中和BoNT血清型B（BoNT/B）-并评估了其在体外和体内的表达。结果证实我们的mRNA在体外和体内表现出良好的表达。此外，一个单一的mRNA脂质纳米粒注射有效地防止BoNT/B体内中毒，效果与蛋白质抗体相当。总之,我们探讨并阐明了编码中和抗体的mRNA药物是否能预防BoNT/B中毒.我们的结果为进一步研究肉毒杆菌毒素中毒的预防和治疗提供了有效的策略。
