在下游加工过程中,水力动力学,机械和界面应激对腺相关病毒血清型8和9的影响
Angela Picciano1, Kelly Wilson1, Katherine Joyner2
1Purification Process Sciences, Biopharmaceutical Development, BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, USA.
Journal of pharmaceutical sciences
|October 6, 2025
概括
制造腺病毒相关病毒 (AAV) 载体涉及身体压力. 运营造成了大量的AAV损失,特别是AAV8,这凸显了对流程优化的需求.
科学领域:
- 生物技术和生物制药制造业
- 基因治疗向量发展发展的基因疗法.
- 病毒载体稳定性研究的研究.
背景情况:
- 基因相关病毒 (AAV) 载体对于基因疗法提供至关重要.
- 在生物加工压力下了解AAV完整性对于产品质量至关重要.
- 制造过程中的物理力量可能会影响病毒载体的性能.
研究的目的:
- 研究生物处理过程中各种物理压力对AAV8和AAV9的影响.
- 评估送,切割速率和其他力量对AAV完整性和称号的影响.
- 确定影响AAV产品质量的关键过程参数.
主要方法:
- 使用缩放模型模拟AAV8和AAV9上的生物处理应力.
- 评估的AAV度,体完整性 (完全与总的比,聚合,碎片),分子量,尺寸,颗粒含量和热稳定性.
- 在不同的物理条件下,量化AAV损失和产品质量指标的变化.
主要成果:
- 送操作导致可溶性AAV度的显著损失,在AAV8.中更为明显.
- 在物理应力下,AAV8表现出更高的颗粒形成倾向.
- 在测试压力下,没有观察到体分子量,尺寸,热稳定性或全对总体比率的显著变化.
- AAV8和AAV9在高剪速 (20,000s-1) 的情况下表现出了显著的稳定性.
结论:
- 抽是一个关键的步骤,需要优化以尽量减少制造过程中的AAV损失.
- AAV病毒载体表现出对抗高剪切力的固有稳定性.
- 精心控制抽取参数对于一致的AAV生物处理和产品产量至关重要.
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