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Current Drug Discovery Technologies
ISSN (Print): 1570-1638
ISSN (Online): 1875-6220
VOLUME: 11
ISSUE: 1
DOI: 10.2174/15701638113109990032









Discovery of Novel Candidate Therapeutics and Diagnostics Based on Engineered Human Antibody Domains

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Author(s): Weizao Chen, Rui Gong, Tianlei Ying, Ponraj Prabakaran, Zhongyu Zhu, Yang Feng and Dimiter S. Dimitrov
Pages 28-40 (13)
Abstract:
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.
Keywords:
Antibody domains, human, library, phage display, scaffold, stability, therapeutics, yeast display.
Affiliation:
Miller Drive, Building 469, Room 150B, Frederick, MD 21702-1201, USA.