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Post-translational Modifications of Recombinant Proteins: Significance for Biopharmaceuticals

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Abstract

The production of recombinant therapeutic proteins is one of the fastest growing sectors of the pharmaceutical industry, particularly monoclonal antibodies and Fc-fusion proteins. Currently, mammalian cells are the dominant production system for these proteins because they can perform complex post-translational modifications that are often required for efficient secretion, drug efficacy, and stability. These protein modifications include misfolding and aggregation, oxidation of methionine, deamidation of asparagine and glutamine, variable glycosylation, and proteolysis. Such modifications not only pose challenges for accurate and consistent bioprocessing, but also may have consequences for the patient in that incorrect modifications and aggregation can lead to an immune response to the therapeutic protein. This mini-review describes examples analytical and preventative advances in the fields of protein oxidation, deamidation, misfolding and aggregation (glycosylation is covered in other articles in this issue). The feasibility of partially replacing traditional analytical methods such as peptide mapping with high-throughput screens and their use in clone and media selection are evaluated. This review also discusses how further technical advances could improve the manufacturability, potency, and safety of biotherapeutics.

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Acknowledgments

The authors wish to thank Prof. Martin Clynes and other members of the National Institute for Cellular Biotechnology (NICB), Dublin City University for the use of their laboratory facilities. The financial support of the Irish Industrial Development Agency (IDA, Ireland) is gratefully acknowledged.

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  1. National Institute for Bioprocessing Research and Training (NIBRT), Engineering Building, University College Dublin, Belfield, Dublin, 4, Ireland

    Nigel Jenkins, Lisa Murphy & Ray Tyther

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  1. Nigel Jenkins
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  2. Lisa Murphy
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Correspondence to Nigel Jenkins.

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Jenkins, N., Murphy, L. & Tyther, R. Post-translational Modifications of Recombinant Proteins: Significance for Biopharmaceuticals. Mol Biotechnol 39, 113–118 (2008). https://doi.org/10.1007/s12033-008-9049-4

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  • DOI: https://doi.org/10.1007/s12033-008-9049-4

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