为AAV8生产开发一个强大且可扩展的平台
André Nascimento1, Tiago Q Faria1, Tiago Nunes1
1iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12, Oeiras 2780-901, Portugal; ITQB-NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República, Oeiras 2780-157, Portugal.
这项研究开发了一种可扩展的腺相关病毒 (AAV) 基因治疗生产平台,从2L到50L尺度实现一致的高产量和产品质量. 过程优化提高了经济效益,而不会影响病毒载体生产效率.
科学领域:
- 生物技术是生物技术.
- 基因治疗制造业 基因治疗制造业
- 病毒载体生产病毒载体生产
背景情况:
- 腺相关病毒 (AAV) 载体对于基因疗法至关重要,需要稳健可扩展的制造工艺.
- 目前对AAV载体的需求需要高效和可重复的生产平台.
研究的目的:
- 设计和实施一个可扩展的AAV8生产平台.
- 验证工艺的稳定性和可扩展性,从实验室到试点规模.
- 在保持产品质量的同时,优化工艺经济性.
主要方法:
- 在2升和50升尺度上进行了三次生产活动.
- 评估上游和下游的过程参数,以获得一致性和产量.
- 评估了关键的修改,包括注射度,核酶选择和直接色谱加载.
主要成果:
- 在各个尺度中实现了一致的标题和恢复率接近80%.
- 验证了成功的可扩展性从2L到50L,而不会损失性能.
- 证明了全片的三倍丰富,表明产品质量更高.
- 在不影响生产的情况下确定了节省成本的修改.
结论:
- 开发的AAV8生产平台是强大的,可扩展的,经济可行的.
- 该过程确保了高产量和产品质量,并有可能在AAV血清型中广泛应用.
- 优化生物处理有助于基因治疗制造业的进步.
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