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Modifications of therapeutic proteins: challenges and prospects

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Abstract

The production of therapeutic proteins is one of the fastest growing sectors of the pharmaceutical industry. However, most proteins used in drug therapy require complex post-translational modifications for efficient secretion, drug efficacy and stability. Common protein modifications include variable glycosylation, misfolding and aggregation, oxidation of methionine, deamidation of asparagine and glutamine, and proteolysis. These modifications not only pose challenges for accurate and consistent bioprocessing, but also may have consequences for the patient in that incorrect modifications or aggregation may lead to an immune response to the protein therapeutic. This review provides examples of analytical and preventative advances that have been devised to meet these challenges, and insights into how further advances can improve the efficiency and safety in manufacturing recombinant proteins.

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Abbreviations

ADCC:

antibody-dependent cellular cytotoxicity

CHO:

Chinese hamster ovary

EPO:

erythropoietin

ESI-MS:

electrospray ionization mass spectrometry

HPLC:

high pressure liquid chromatography

MALDI:

matrix-assisted laser desorption-ionization

PTM:

post-translational modification

UDP:

uridine-5′-diphosphate

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Authors and Affiliations

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

    Nigel Jenkins

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  1. Nigel Jenkins
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Correspondence to Nigel Jenkins.

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Jenkins, N. Modifications of therapeutic proteins: challenges and prospects. Cytotechnology 53, 121–125 (2007). https://doi.org/10.1007/s10616-007-9075-2

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  • DOI: https://doi.org/10.1007/s10616-007-9075-2

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