稳定且可重复使用的对有反应的生物聚合物,用于治疗抗体的亲和沉
Heesun Park1,2, Jeong-Seok Oh2, Jonghwan Lee1
1Center for Convergence Bioceramic Materials, Korea Institute of Ceramic Engineering and Technology, Cheongjusi, Chungcheongbuk-do, South Korea.
Protein science : a publication of the Protein Society
|July 29, 2024
概括
一种新的融合蛋白,ZZ-4N-hCSQ1,通过提高稳定性和降低成本来增强抗体净化. 与传统的蛋白质A染色体相比,这种方法提供了更高的纯度和成本效益,用于治疗性抗体生产.
科学领域:
- 生物技术是生物技术.
- 蛋白质工程是指蛋白质工程.
- 生物加工是一种生物加工.
背景情况:
- 亲和沉为蛋白质净化提供了优势,包括速度和特异性.
- 之前的ZZ-hCSQ2融合蛋白在工业抗体净化中表现出稳定性的局限性,在10次重复使用后产量下降.
研究的目的:
- 开发一种更稳定,更强大的融合蛋白,用于抗体净化.
- 提高治疗性抗体生产的效率和成本效益.
主要方法:
- 计算的罗塞塔能量值,以评估calsequestrin (CSQ) 同类物的折叠稳定性.
- 为其稳定性选择了人类的CSQ1 (hCSQ1),并将链接序列修改为四个阿斯巴拉金 (4N) 残留物.
- 在各种条件下测试了新的ZZ-4N-hCSQ1融合蛋白的稳定性和可重复使用性.
主要成果:
- 在含有蛋白酶的介质和高pH条件下,ZZ-4N-hCSQ1融合蛋白在5天以上的时间内显示出高稳定性.
- 在没有损失回收率的情况下,实现了至少25次抗体净化重复使用.
- 纯化抗体的纯度显著更高,与蛋白质A染色体相比,宿主细胞DNA和蛋白质污染率较低.
结论:
- ZZ-4N-hCSQ1沉是一种高效和稳定的抗体净化方法.
- 这种方法具有显著的成本效益,可能比现有技术便宜高达12.5倍.
- 改进的净化过程可以降低治疗抗体的生产成本.
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