基于固定床生物反应器的AAV生产的多变量过程优化提高了总批次产量
Ruchita Selot1, Ashish Khaparde1, Sharath Babu G R1
1GROW Research Laboratory, Narayana Netralaya Foundation, Bengaluru, India.
Human gene therapy
|November 24, 2025
概括
优化固定床生物反应器参数显著提高了腺相关病毒载体 (AAV) 生产. 这项研究实现了病毒产量的7.6倍增加,为可扩展的基因疗法制造铺平了道路.
科学领域:
- 生物技术是生物技术.
- 基因治疗 基因治疗
- 生物加工是一种生物加工.
背景情况:
- 基因相关病毒载体 (AAV) 对基因疗法至关重要,但面临着生产可扩展性的挑战.
- 高质量,高产量的AAV生产对于临床应用至关重要.
研究的目的:
- 在固定床生物反应器中优化腺相关病毒载体 (AAV) 生产.
- 为了提高AAV产量和基因治疗应用的可扩展性.
主要方法:
- 在固定床生物反应器中系统优化细胞播种密度,转染密度和DNA与细胞的比率.
- 在附着的HEK-293T细胞,包装记者和治疗基因中利用过渡转染成AAV9囊体.
- 在10天的生产周期中监测了生物反应器的关键参数 (pH,溶氧,葡萄糖).
主要成果:
- 在固定床生物反应器中,达到高达3 × 10^9细胞/m2的细胞密度.
- 与原型批量相比,病毒产量增加了大约7.6倍.
- 获得了2.3 × 10^14 vg的平均AAV矢量产量,每个细胞的平均产量为1.4 × 10^5 vg/细胞.
结论:
- 固定床生物反应器中优化过程参数是可扩展的AAV生产的可行策略.
- 这种方法为为临床试验的AAV载体的成本效益制造提供了一个有前途的途径.
- 优化的过程支持高细胞密度,并显著提高病毒产量.
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