Glycosylation: impact, control and improvement during therapeutic protein production

Crit Rev Biotechnol. 2014 Dec;34(4):281-99. doi: 10.3109/07388551.2013.793649. Epub 2013 Aug 6.

Abstract

The emergence of the biopharmaceutical industry represented a major revolution for modern medicine, through the development of recombinant therapeutic proteins that brought new hope for many patients with previously untreatable diseases. There is a ever-growing demand for these therapeutics that forces a constant technological evolution to increase product yields while simultaneously reducing costs. However, the process changes made for this purpose may also affect the quality of the product, a factor that was initially overlooked but which is now a major focus of concern. Of the many properties determining product quality, glycosylation is regarded as one of the most important, influencing, for example, the biological activity, serum half-life and immunogenicity of the protein. Consequently, monitoring and control of glycosylation is now critical in biopharmaceutical manufacturing and a requirement of regulatory agencies. A rapid evolution is being observed in this context, concerning the influence of glycosylation in the efficacy of different therapeutic proteins, the impact on glycosylation of a diversity of parameters/processes involved in therapeutic protein production, the analytical methodologies employed for glycosylation monitoring and control, as well as strategies that are being explored to use this property to improve therapeutic protein efficacy (glycoengineering). This work reviews the main findings on these subjects, providing an up-to-date source of information to support further studies.

Keywords: Analytical methodologies; culture parameters; expression system; glycoengineering; mammalian cells; process development.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antibodies, Monoclonal* / chemistry
  • Antibodies, Monoclonal* / metabolism
  • Bioreactors*
  • Cells, Cultured
  • Glycosylation*
  • Humans
  • Plants / genetics
  • Plants / metabolism
  • Protein Engineering*
  • Recombinant Proteins* / chemistry
  • Recombinant Proteins* / metabolism
  • Yeasts / genetics
  • Yeasts / metabolism

Substances

  • Antibodies, Monoclonal
  • Recombinant Proteins