Discovery of Novel Candidate Therapeutics and Diagnostics Based on Engineered Human Antibody Domains
Weizao Chen, Rui Gong, Tianlei Ying, Ponraj Prabakaran, Zhongyu Zhu, Yang Feng and Dimiter S. Dimitrov
Affiliation: Miller Drive, Building 469, Room 150B, Frederick, MD 21702-1201, USA.
Keywords: Antibody domains, human, library, phage display, scaffold, stability, therapeutics, yeast display.
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.
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