通过使用高通量树脂尖端模块加速AAV净化过程的开发
Qingxuan Li1, Mahsa Hadidi1, Steven Benner2
1Sanofi Genomic Medicine Unit, CMC, Purification Process Development, Waltham, Massachusetts, USA.
Biotechnology progress
|July 18, 2025
概括
开发高吞吐量 (HTP) 方法加速了腺相关病毒 (AAV) 净化. 使用树脂尖端和分析工具的集成HTP工作流程大大降低了基因疗法开发的材料要求和成本.
科学领域:
- 生物技术是生物技术.
- 基因治疗 基因治疗
- 过程开发 过程开发
背景情况:
- 重组腺相关病毒 (AAV) 是基因治疗的关键交付工具,需要强大的净化过程.
- AAV净化面临的挑战包括有限的材料,高成本和紧张的时间表,特别是在早期的开发阶段.
- 高吞吐量 (HTP) 方法为克服这些净化开发障碍提供了解决方案.
研究的目的:
- 建议和验证一个集成的端到端HTP工作流程,以加速AAV净化过程的开发.
- 为了证明HTP方法在确定最小样本输入的净化参数方面的效率.
- 评估HTP工作流对AAV质量属性和商品成本的影响.
主要方法:
- 开发一个集成的HTP工作流程,使用树脂尖端净化模块和HTP分析工具包.
- 使用微量样本 (25μL树脂尖端) 选净化参数 (结合能力,树脂选择,缓冲成分).
- 应用HTP工作流程用于AAV质量属性评估和与基准方法 (Robocolumn) 的比较.
主要成果:
- 有效地确定净化参数,用微体样分离AAV全,部分和空体.
- 成功地预测了基缩和部分基除的趋势,用于基板级净化.
- 证明了与基准方法相比较的AAV质量属性,材料量显著减少 (基准的2%).
结论:
- 集成的HTP工作流通过利用HTP分析工具来快速解释数据,有效地加速了AAV净化过程的开发.
- 这种方法显著减少了材料需求,缩短了分析周转时间,并提供了大量的商品成本节省.
- 经过验证的HTP工作流对于推动早期基因疗法开发至关重要,因为它能够有效地净化AAV和质量评估.
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