针对性序列捕获 (TSC) 的应用用于产生抗体的细胞系的遗传特征
Sofie A O'Brien1, Jake T Leinas1, Jodi Grantham1
1Bioprocess Research and Development, Pfizer Inc., Bothell, Washington, USA.
Biotechnology journal
|February 12, 2026
概括
下一代测序 (NGS) 提供了一种强大的方法来评估生物治疗生产细胞系在发育早期的遗传稳定性. 这种方法确保了基因可比性,减少了用于商业制造的细胞系选择相关的风险.
科学领域:
- 生物技术是生物技术.
- 分子生物学分子生物学
- 生物制药制造业 生物制药制造业
背景情况:
- 监管机构要求生物治疗药物商业许可证生产细胞系的基因可比性.
- 早期细胞系发育 (CLD) 在良好的制造工艺 (GMP) 细胞库用于遗传特征的可用性之前.
- 在早期的CLD中评估遗传稳定性至关重要,以防止不稳定的细胞系的选择.
研究的目的:
- 开发和验证基于下一代测序 (NGS) 的方法来评估细胞系遗传稳定性.
- 实施新的生物信息分析,以进行全面的遗传表征.
- 为了能够在细胞系发育过程中早期确定遗传稳定性.
主要方法:
- 开发一个使用NGS的目标序列捕获 (TSC) 管道.
- 应用TSC管道到82个克隆衍生抗体生产的中国汉姆斯特卵巢 (CHO) 细胞系.
- 基因组转基因序列身份,整合位点,矢量完整性和复制号码的表征.
主要成果:
- 基于NGS的方法提供了早期评估CHO细胞系的遗传稳定性.
- 通过NGS确定的基因稳定性与使用GMP细胞库的传统方法相比.
- 演示了NGS用于表征集成向量序列和副本编号的实用性.
结论:
- 在生物治疗制造生命周期的早期,NGS是建立基因稳定的宝贵工具.
- NGS提供了一种适合和有效的方法,用于生产细胞系的遗传特征.
- 使用NGS进行早期遗传稳定性评估可以降低指定遗传不稳定的细胞系的风险.
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