治疗抗体-siRNA结合物的极性和序列依赖性电离:为全面的特征和身份释放试验提供完整的多属性方法
Hao Liu1, Jamie L Veltri1, P Clayton Gough1
1Bioproduct Research and Development, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana 46285, United States.
Analytical chemistry
|February 27, 2026
概括
使用SEC-MS的新型完整多属性方法 (iMAM) 能够有效地表征抗体-siRNA结合物 (ARC). 该方法监测ARC制造和发布的关键质量属性,确保产品质量和一致性.
科学领域:
- 生物结合化学 生物结合化学
- 分析化学 分析化学
- 制药科学 制药科学
背景情况:
- 抗体-siRNA合物 (ARCs) 是针对小干扰性核糖核酸 (siRNAs) 的向输送的先进疗法.
- 描述复杂的ARC和监测它们的关键质量属性 (CQA) 在开发和制造过程中提出了重大分析挑战.
- 强大的分析方法对于确保基于ARC的治疗方法的安全性,有效性和一致性至关重要.
研究的目的:
- 开发和资格的新的分析方法,以全面的ARCs的特征.
- 在良好制造实践 (GMP) 环境中建立一个可靠的方法来监测ARC的CQAs.
- 在质谱分析过程中获得关于ARCs电离行为的基本见解.
主要方法:
- 开发一个完整的多属性方法 (iMAM),使用原生尺寸排除色谱-质谱法 (SEC-MS).
- 对iMAM作为ARC药物物质 (DS) 和药物产品 (DP) 的身份释放试验的评估和资格.
- 调查质谱运行极性对siRNA完整性和ARC电离化的影响.
主要成果:
- iMAM成功监测了各种CQAs,包括身份,纯度,HMWS,LMWS,N-糖化和药物对抗体比 (DAR).
- 积极的MS极性保留了更多的siRNA复合体,而负极性显示了更多的ARC单链RNA.
- 在离子化过程中,抗体的存在保护了siRNA复合体,其复合比与siRNA的GC含量和Tm相关.
结论:
- 合格的iMAM提供了一种简单,有效和符合GMP的ARC特性和释放测试方法.
- 了解MS极性对ARC的影响有助于优化复杂生物结合物的分析策略.
- 这些发现有助于对ARC电离的基本知识,促进改进分析方法的开发.
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