School of Medical Device, Shenyang Pharmaceutical University, Shenyang, Liaoning, China.
Protein Engineering Laboratory, Beijing Institute of Biotechnology, Beijing, China.
Hum Vaccin Immunother. 2024 Dec 31;20(1):2358570. doi: 10.1080/21645515.2024.2358570. Epub 2024 Jun 9.
Among all natural and synthetic toxins, botulinum neurotoxins (BoNTs), produced by 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.
在所有天然和合成毒素中，由 在厌氧环境中产生的肉毒神经毒素（BoNTs）是最毒的聚合物蛋白。目前，预防和治疗肉毒中毒最有效的方法分别是接种疫苗和使用抗毒素。然而，这些方法与主动免疫的长反应时间、副作用和供体限制有关。因此，有必要开发更有前途的肉毒中毒预防和治疗方法。在这里，我们设计了一种编码 B9-hFc 的 mRNA - 一种与人 Fc 融合的 VHH 重链抗体，可有效中和 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 在体外和体内均具有良好的表达。此外，单次 mRNA 脂质纳米颗粒注射可有效预防 BoNT/B 中毒，其效果可与蛋白质抗体相媲美。总之，我们探讨并阐明了编码中和抗体的 mRNA 药物是否可预防 BoNT/B 中毒。我们的结果为进一步研究肉毒毒素中毒的预防和治疗提供了一种有效的策略。
