The concept of engineering robust protein scaffolds for novel binding functions emerged 20 years ago, one decade after the advent of recombinant antibody technology. Early examples were the Affibody, Monobody (Adnectin), and Anticalin proteins, which were derived from fragments of streptococcal protein A, from the tenth type III domain of human fibronectin, and from natural lipocalin proteins, respectively. Since then, this concept has expanded considerably, including many other protein templates. In fact, engineered protein scaffolds with useful binding specificities, mostly directed against targets of biomedical relevance, constitute an area of active research today, which has yielded versatile reagents as laboratory tools. However, despite strong interest from basic science, only a handful of those protein scaffolds have undergone biopharmaceutical development up to the clinical stage. This includes the abovementioned pioneering examples as well as designed ankyrin repeat proteins (DARPins). Here we review the current state and clinical validation of these next-generation therapeutics.

中文翻译：

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工程蛋白支架作为下一代疗法。

重组抗体技术问世十年后的20年前，人们就提出了为新的结合功能设计强大的蛋白质支架的构想。早期的例子是Affibody，Monobody（Adnectin）和Anticalin蛋白，它们分别来自链球菌蛋白A的片段，人纤连蛋白的第十个III型结构域和天然lipocalin蛋白。从那时起，这个概念有了很大的扩展，包括许多其他蛋白质模板。实际上，具有有用结合特异性的工程化蛋白支架（主要针对生物医学相关靶标）构成了当今活跃的研究领域，已产生了用作实验室工具的多功能试剂。但是，尽管基础科学引起了浓厚的兴趣，直到临床阶段，这些蛋白质支架中只有少数经历了生物药物开发。这包括上述开创性的例子以及设计的锚蛋白重复蛋白（DARPins）。在这里，我们回顾了这些下一代疗法的当前状态和临床验证。