对寡核酸二元体的表征的新兴趋势
Alexandre Goyon1, Daniel Ngoc Nguyen1, Kelly Zhang1
1Synthetic Molecule Pharmaceutical Sciences, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
Journal of chromatography. A
|September 2, 2025
概括
治疗性寡核酸二聚体的特征是复杂的. 离子移动性质谱和HILIC的近期进展提供了新的分析方法,但在识别形配置和改进分离方面仍然存在挑战.
科学领域:
- 分析化学
- 制药科学
- 生物技术
背景情况:
- 化学修饰增强了寡核酸治疗效果,但使分析复杂化.
- 用酸 (PS) 修饰的寡核酸形成复杂的二聚体混合物,需要强大的分析方法.
- 监管机构要求对寡核酸药物进行准确的二元体分布和批量复制性.
研究的目的:
- 批判性地审查最新的技术 (2023年以后) 用于分析寡核酸二聚体.
- 突出描述PS改性治疗性寡核酸的持续挑战.
- 在理解寡核酸二聚合物复杂性方面的分析差距.
主要方法:
- 对寡核酸二聚体的分析技术的最新文献的审查.
- 专注于离子移动性质谱学 (IM-MS) 和水友交互液体色谱学 (HILIC).
- 检查用于识别PS连接的奇拉性配置 (Sp/Rp) 的方法.
主要成果:
- 尽管采用了新技术,但最大可分离的二聚体数量 (32) 的改进有限.
- IM-MS和HILIC显示出有希望的结果,但在全面的二元体表征方面面临挑战.
- 目前正在进行的研究旨在改善PS链接立体化学的识别.
结论:
- 治疗性寡核酸二聚体的分析特征仍然是一个重大挑战.
- 在IM-MS和HILIC方面取得的进展至关重要,但需要进一步开发才能完全分离和识别二聚体.
- 解决这些分析缺陷对于安全有效地使用寡核酸治疗药物至关重要.
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