在人体血和血清中通过尺寸排除色谱加上双角度光散射技术对mRNA-脂质纳米颗粒稳定性的定量分析
Brian Liau1, Li Zhang2, Melgious Jin Yan Ang2
1Agilent Technologies, 1 Yishun Avenue 7, Singapore 768923, Republic of Singapore.
Nanomedicine : nanotechnology, biology, and medicine
|March 18, 2024
概括
使用多角度光散射 (SEC-MALS) 的尺寸排除色谱有效评估mRNA-LNP在血清和血中的稳定性. 在ALC-0315中的微量杂质显著降低了mRNA-LNP稳定性,突出了SEC-MALS用于质量控制.
科学领域:
- 生物技术是生物技术.
- 纳米医学是一种纳米医学.
- 分析化学 分析化学
背景情况:
- 脂质纳米颗粒 (LNP) 对于传递信使RNA (mRNA) 疗法至关重要.
- 评估生物流体中的mRNA-LNP稳定性对于临床翻译至关重要.
- 像动态光散射这样的传统方法在复杂矩阵中存在局限性.
研究的目的:
- 引入与多角度光散射 (SEC-MALS) 结合的大小排除色谱作为评估mRNA-LNP稳定性的新方法.
- 研究人类血清和血对mRNA-LNP完整性的影响.
- 确定影响mRNA-LNP稳定性的因素,包括配方杂质.
主要方法:
- 使用尺寸排除色谱与双角度光散射相结合 (SEC-MALS).
- 采用双列配置,以最大限度地减少血清和血成分的干扰.
- 分析了mRNA-LNP分子重量和旋转半径的随时间变化.
主要成果:
- SEC-MALS准确地确定了mRNA-LNP降解动力学和血清和血中的物理性质变化.
- 血清和血对mRNA-LNP大小和分子量表现出明显的影响,这表明凝固因子的参与.
- 在ALC-0315 (O-tert-butyloxycarbonyl-protected形式) 中~1%的杂质被确定为降低血清mRNA-LNP稳定性的关键因素.
结论:
- SEC-MALS是评估复杂生物矩阵中mRNA-LNP稳定性的强大工具.
- 了解生物流体的影响和配方纯度对于开发稳定的mRNA-LNP疗法至关重要.
- 这些发现支持使用SEC-MALS进行质量控制和优化LNP配方.
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