Casteleijn Marco G, Abendroth Ulrike, Zemella Anne, Walter Ruben, Rashmi Rashmi, Haag Rainer, Kubick Stefan
VTT Technical Research Centre of Finland Ltd, 02150 Espoo, Finland.
Fraunhofer Institute for Cell Therapy and Immunology (IZI), Branch Bioanalytics and Bioprocesses (IZI-BB), Am Mühlenberg, 14476 Potsdam, Germany.
Chem Rev. 2025 Feb 12;125(3):1303-1331. doi: 10.1021/acs.chemrev.4c00126. Epub 2025 Jan 22.
Throughout history, we have looked to nature to discover and copy pharmaceutical solutions to prevent and heal diseases. Due to the advances in metabolic engineering and the production of pharmaceutical proteins in different host cells, we have moved from mimicking nature to the delicate engineering of cells and proteins. We can now produce novel drug molecules, which are fusions of small chemical drugs and proteins. Currently we are at the brink of yet another step to venture beyond nature's border with the use of unnatural amino acids and manufacturing without the use of living cells using cell-free systems. In this review, we summarize the progress and limitations of the last decades in the development of pharmaceutical protein development, production in cells, and cell-free systems. We also discuss possible future directions of the field.
纵观历史，我们一直指望从自然界中发现并复制预防和治疗疾病的药物解决方案。由于代谢工程的进步以及在不同宿主细胞中生产药用蛋白质，我们已经从模仿自然转向对细胞和蛋白质进行精细工程改造。现在我们能够生产新型药物分子，它们是小分子化学药物与蛋白质的融合体。目前，我们正处于迈向另一个阶段的边缘，即利用非天然氨基酸并使用无细胞系统在不使用活细胞的情况下进行制造，从而突破自然的界限。在这篇综述中，我们总结了过去几十年在药用蛋白质开发、细胞生产和无细胞系统方面的进展与局限。我们还讨论了该领域未来可能的发展方向。
