腺相关病毒输液增强表达:一种商业上可扩展的,高标位的,高质量的生产细胞系过程
Wei Xue1, Cameron Fulco1, Sha Sha1
1Ultragenyx Pharmaceutical Inc., Global CMC Development, 19 Presidential Way, Woburn, MA 01801, USA.
Molecular therapy. Methods & clinical development
|June 13, 2024
概括
再组合腺相关病毒 (rAAV) 是基因治疗的关键载体. 一种新的AAV输液增强表达 (APEX) 过程显著提高了rAAV的产生,改善了罕见疾病治疗的产量和可扩展性.
科学领域:
- 基因治疗 基因治疗
- 生物技术是生物技术.
- 罕见疾病治疗方法 罕见疾病治疗方法
背景情况:
- 再组合腺相关病毒 (rAAVs) 是罕见的,单源性疾病的主要基因转移载体,在30多年中已证明其安全性和有效性.
- 尽管取得了进展,但rAAV生产的良好制造实践 (GMP) 仍然存在挑战,包括产量,成本,可扩展性和质量.
- 目前的过渡性传染方法在产量,成本,稳定性和可扩展性方面存在局限性,阻碍了可靠的全球患者访问.
研究的目的:
- 为rAAV载体引入和评估一种新的制造工艺.
- 为了应对rAAV生产产量,成本和可扩展性的持续挑战.
- 增强可靠的RAAV产品供应,以实现更广泛的患者获取.
主要方法:
- 开发和实施一种新的AAV输液增强表达 (APEX) 过程.
- 利用稳定的生产者细胞线来提高可扩展性和生产力.
- 在多种rAAV血清型中大规模细胞培养中展示APEX过程.
主要成果:
- 在生产生物反应器中,APEX工艺实现了更高的最大细胞密度.
- 与现有方法相比,观察到体积生产率增加了3到6倍.
- 获得了接近1 x 10^12 GC/mL的标位,证明了高产量生产.
结论:
- APEX生产平台代表了rAAV制造的重大进步.
- 这种新的工艺提高了rAAV载体生产的效率和有效性.
- APEX过程有望改善对罕见疾病的基因疗法的可靠和可扩展的供应.
关键词:
在 AAV AAV AAV 中.细胞密度的影响生产成本的生产成本.高收益的高收益产品perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion perfusion 这是一个非常重要的方法,它可以让一个人成为一个非常重要的角色,一个非常重要的角色,一个非常重要的角色,一个非常重要的角色,一个非常重要的角色,一个非常重要的角色,一个非常重要的角色,一个非常重要的角色发展过程发展过程.生产者细胞线生产者细胞线可扩展的可扩展的可扩展.
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