胰岛素进化:对复合生产进步的整体观点
Ansuman Sahoo1, Prabir Kumar Das1, Veeranki Venkata Dasu1
1Biochemical Engineering Laboratory, Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, 781039, Assam, India.
International journal of biological macromolecules
|July 20, 2024
概括
糖尿病率的上升和口服胰岛素的需求需要改善复合人体胰岛素的生产. 本综述探讨了上游和下游的生物工艺策略,以克服包容性机构和负担得起的胰岛素高成本等挑战.
科学领域:
- 生物技术和制药科学 生物技术和制药科学
- 代谢障碍和内分泌学
背景情况:
- 全球糖尿病患病率的增加和对包括口服胰岛素在内的可获得胰岛素疗法的需求,突显出需要高效的复合人体胰岛素 (rHI) 生产.
- 40多年前开发的现有的rHI表达系统面临诸如包容体形成,使用有毒诱导剂和高生产成本等挑战.
- 当前胰岛素生产方法的局限性影响了可负担性和可访问性,需要生物处理的进步.
研究的目的:
- 审查和分析用于复合人胰岛素生物生产的上游和下游阶段的各种策略.
- 确定和讨论克服胰岛素制造现有瓶的方法,重点是提高效率和降低成本.
- 检查用于确保复合人胰岛素真实性和纯度的分析技术.
主要方法:
- 探索各种表达系统,包括细菌,酵母,转基因植物/动物,哺乳动物细胞系和无细胞系统用于rHI生产.
- 对上游策略的分析,如双链,亲胰岛素,迷你亲胰岛素,与融合蛋白的亲胰岛素,护卫者,信号和净化标签的利用.
- 对下游加工技术的审查侧重于恢复完整,生物活性和纯复合人体胰岛素.
主要成果:
- 目前正在研究多个表达平台和蛋白质工程方法,以提高rHI产量和质量.
- 优化上游 (表达) 和下游 (净化) 过程对于具有成本效益和大规模的胰岛素制造至关重要.
- 有一系列的分析方法可用于验证产生的复合人胰岛素的身份,纯度和生物活性.
结论:
- 解决当前重组人体胰岛素生产系统面临的挑战对于满足未来的全球需求和确保可负担性至关重要.
- 集成先进的上游和下游生物处理技术,加上强大的分析验证,是成功制造胰岛素的关键.
- 对表达系统和净化策略的持续创新对于再生组合人胰岛素的可持续和经济生产至关重要.
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