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.
Current Drug Discovery Technologies
Title:Discovery of Novel Candidate Therapeutics and Diagnostics Based on Engineered Human Antibody Domains
Volume: 11 Issue: 1
Author(s): Weizao Chen, Rui Gong, Tianlei Ying, Ponraj Prabakaran, Zhongyu Zhu, Yang Feng and Dimiter S. Dimitrov
Affiliation:
Keywords: Antibody domains, human, library, phage display, scaffold, stability, therapeutics, yeast display.
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.
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Cite this article as:
Chen Weizao, Gong Rui, Ying Tianlei, Prabakaran Ponraj, Zhu Zhongyu, Feng Yang and Dimitrov S. Dimiter, Discovery of Novel Candidate Therapeutics and Diagnostics Based on Engineered Human Antibody Domains, Current Drug Discovery Technologies 2014; 11 (1) . https://dx.doi.org/10.2174/15701638113109990032
DOI https://dx.doi.org/10.2174/15701638113109990032 |
Print ISSN 1570-1638 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-6220 |
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