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Synthetic therapeutic antibodies

Nature Chemical Biology volume 2, pages 682–688 (2006)Cite this article

Abstract

Advances in selection technologies have sped up the process of generating antibodies with exquisitely tailored characteristics. In particular, synthetic antibody libraries, in which the antigen-binding sites are entirely man-made, have come of age and now rival or even exceed the potential of natural immune repertoires. Control over both library design and selection conditions enables unprecedented precision in antibody engineering. Synthetic libraries have been used to gain insights into the mechanisms of antibody structure and function, to tackle particularly difficult therapeutic challenges and to expand the utility of antibodies to novel areas of research.

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Figure 1: Construction of antibody libraries from natural or synthetic diversity.
Figure 2: Sites of diversification in synthetic antibody libraries.
Figure 3: The structural epitopes for VEGFR1 and antibodies binding to human VEGF.
Figure 4: Minimalist antigen-binding sites are dominated by tyrosine.

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Authors and Affiliations

  1. the Department of Protein Engineering, Genentech Inc., 1 DNA Way, South San Francisco, 94080, California, USA

    Sachdev S Sidhu

  2. Frederic A. Fellouse is at the Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue, Toronto, M5G 1X5, Ontario, Canada

    Frederic A Fellouse

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  1. Sachdev S Sidhu
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Correspondence to Sachdev S Sidhu.

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Competing interests

The authors are employed by Genentech, Inc., which develops antibody therapeutics for the health care market.

Supplementary information

Supplementary Table 1

Highly functional synthetic antibody libraries. (PDF 20 kb)

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Sidhu, S., Fellouse, F. Synthetic therapeutic antibodies. Nat Chem Biol 2, 682–688 (2006). https://doi.org/10.1038/nchembio843

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