应用iPLUS非编码序列来改善生物制药生产
Inês Reis-Claro1, Maria Inês Silva1, Ana Moutinho1
1Gene Regulation, i3S-Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Porto, Portugal.
Frontiers in bioengineering and biotechnology
|February 21, 2024
概括
一个新的调节元件,iPLUS,显著提高了重组蛋白和mRNA的生产. 这一发现提高了在各种系统中生产生物治疗药物的效率,包括单克隆抗体和mRNA疫苗.
科学领域:
- 生物技术和生物制药生产
- 分子生物学和基因表达规范
背景情况:
- 生物技术领域正在迅速扩大,重点是用于治疗应用的重组蛋白质生产.
- 3'非翻译区域 (3'UTR) 的cis-regulatory元素在控制mRNA和蛋白质表达水平方面发挥着至关重要的作用.
研究的目的:
- 调查3'UTR cis调节元件在提高生物疗法的mRNA和蛋白质水平中的功能.
- 探索一种通用序列的调节潜力,iPLUS,用于增加重组蛋白质的生产.
主要方法:
- 将 iPLUS 序列纳入单克隆抗体和记者蛋白的表达载体.
- 使用哺乳动物细胞系 (ExpiCHO) 和酵母Pichia pastoris进行蛋白质生产实验.
- 评估了iPLUS及其变体 (iPLUSv2) 对mRNA和蛋白质水平在mRNA疫苗环境中的影响 (Spike,MAGEC2).
主要成果:
- 在ExpiCHO细胞中,iPLUS使得trastuzumab的产量增加了2倍.
- 在Pichia pastoris中,iPLUS (3x) 和iPLUSv2可在100倍以上的时间内增强记者蛋白的产生.
- 在mRNA疫苗应用中,iPLUSv2使斯派克和MAGEC2的产量翻了一番.
结论:
- iPLUS序列是一种多功能工具,可在多种生物系统中显著增加重组蛋白和mRNA水平.
- iPLUS展示了其作为优化生物制药行业生产流程的宝贵资产的潜力,包括mRNA疫苗.
- 这项研究强调了非编码序列在生物制造中的基因表达控制中的重要性.
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