Chen Weizao, Gong Rui, Ying Tianlei, Prabakaran Ponraj, Zhu Zhongyu, Feng Yang, Dimitrov Dimiter S
Miller Drive, Building 469, Room 150B, Frederick, MD 21702-1201, USA.
Curr Drug Discov Technol. 2014 Mar;11(1):28-40. doi: 10.2174/15701638113109990032.
The smallest independently folded antibody fragments, the domains, are emerging as promising scaffolds for candidate therapeutics and diagnostics that bind specifically targets of interest. The discovery of such binders is based on several technologies including structure-based design and generation of libraries of mutants displayed on phage or yeast, next-generation sequencing for diversity analysis, panning and screening of the libraries, affinity maturation of selected binders, and their expression, purification, and characterization for specific binding, function, and aggregation propensity. In this review, we describe these technologies as applied for the generation of engineered antibody domains (eAds), especially those derived from the human immunoglobulin heavy chain variable region (VH) and the second domain of IgG1 heavy chain constant region (CH2) as potential candidate therapeutics and diagnostics, and discuss examples of eAds against HIV-1 and cancer-related proteins.
最小的独立折叠抗体片段，即结构域，正成为用于候选治疗药物和诊断试剂的有前景的支架，这些药物和试剂能特异性结合感兴趣的靶点。此类结合物的发现基于多种技术，包括基于结构的设计以及在噬菌体或酵母上展示的突变体文库的构建、用于多样性分析的新一代测序、文库的淘选和筛选、所选结合物的亲和力成熟，以及它们的表达、纯化和针对特异性结合、功能及聚集倾向的表征。在本综述中，我们描述了这些应用于工程化抗体结构域（eAds）生成的技术，特别是那些源自人免疫球蛋白重链可变区（VH）和IgG1重链恒定区第二结构域（CH2）的结构域作为潜在的候选治疗药物和诊断试剂，并讨论了针对HIV-1和癌症相关蛋白的eAds实例。
