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Single Domain Antibody Fragments as Drug Surrogates Targeting Protein–Protein Interactions inside Cells
MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford, OX3 9DS, UK
Dainippon Sumitomo Pharma Co., Ltd., Genomic Science Laboratories, 3-1-98 Kasugade-naka, Konohana-ku, Osaka 544-0022, Japan
* Author to whom correspondence should be addressed.
Received: 3 April 2013; in revised form: 23 April 2013 / Accepted: 24 April 2013 / Published: 2 May 2013
Abstract: Many human diseases are caused by mutant or abnormal protein functions that are largely confined to the inside of cells, rather than being displayed on the abnormal cell surface. Furthermore, many of the functional consequences of aberrant proteins, such as in cancer cells, are due to protein–protein interactions (PPIs). Developing reagents that can specifically interfere with PPI is an important goal for both therapeutic use and as reagents to interrogate the functional importance of PPI. Antibody fragments can be used for inhibiting PPI. Our recent technology development has provided a set of simple protocols that allow development of single antibody variable (V) region domains that can function inside the reducing environment of the cell. The heavy chain variable region (VH) segments mainly used in this technology are based on a designer framework that folds inside cells without the need for the intra-chain disulphide bond and can be used as drug surrogates to determine on-target effects (target validation) and as templates for small molecule drug development. In this review, we discuss our work on single domains as intracellular antibodies and where this work might in the future.
Keywords: immunoglobulin; antibody; intracellular; VH; PPI; therapy; macrodrug
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Cite This Article
MDPI and ACS Style
Zeng, J.; Zhang, J.; Tanaka, T.; Rabbitts, T.H. Single Domain Antibody Fragments as Drug Surrogates Targeting Protein–Protein Interactions inside Cells. Antibodies 2013, 2, 306-320.
Zeng J, Zhang J, Tanaka T, Rabbitts TH. Single Domain Antibody Fragments as Drug Surrogates Targeting Protein–Protein Interactions inside Cells. Antibodies. 2013; 2(2):306-320.
Zeng, Jia; Zhang, Jing; Tanaka, Tomoyuki; Rabbitts, Terence H. 2013. "Single Domain Antibody Fragments as Drug Surrogates Targeting Protein–Protein Interactions inside Cells." Antibodies 2, no. 2: 306-320.