数字双胞胎mRNA的基础In Vitro 转录在可变规模向自主操作转变
Alina Hengelbrock1, Axel Schmidt1, Jochen Strube1
1Institute for Separation and Process Technology, Clausthal University of Technology, Clausthal-Zellerfeld 38678, Germany.
ACS omega
|February 26, 2024
概括
通过先进的体外转录方法优化信使核糖核酸 (mRNA) 生产,产量增加了55%,并减少了副产品. 这种可扩展的机器学习方法可以快速选和制造mRNA疫苗和疗法.
科学领域:
- 生物技术是生物技术.
- 生物工艺工程 生物工艺工程
- 分子生物学分子生物学
背景情况:
- COVID-19大流行凸显了mRNA疫苗和治疗开发的挑战,包括制造缺陷和公平分配问题.
- 由于有效性,安全性和制造限制,大量基于RNA的候选药物失败,影响流行病应对.
- 优化信使核糖核酸 (mRNA) 生产对于开发有效的疫苗和疗法至关重要.
研究的目的:
- 使用可扩展的机器优化mRNA的体外转录,以提高生产效率和产量.
- 研究mRNA生产的关键机制,以改善疫苗和治疗开发.
- 为了证明mRNA和其他细胞和基因治疗候选人的连续制造过程.
主要方法:
- 用可扩展的机器确定mRNA生产的动力参数.
- 确定了优化的反应条件 (温度,尿素度,添加剂),以最大限度地提高mRNA产量.
- 针对候选疫苗的高通量查 (HTS) 使用了细分流程方法.
主要成果:
- 优化条件导致mRNA产量增加了55%,截断的mRNA减少了33%.
- 细分流程方法使得20个候选疫苗的生产成为可能,与非细分反应相比,提高了生产率十倍.
- 该研究表明,在连续运行中使用相同的设备进行查和制造各种候选药物的可行性.
结论:
- 开发的过程显著提高了mRNA生产产量和纯度,解决了关键的制造缺陷.
- 集成可扩展的机器和细分流量方法可促进高吞吐量查和mRNA疗法的连续制造.
- 这种方法有助于为公共卫生紧急情况提供更快速,更有弹性和更公平的基于mRNA的关键疫苗和疗法.
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