Mammalian cells are frequently selected as expression systems for protein biopharmaceuticals because of their ability to produce proteins with ‘human-like’ post-translational modifications. The structure of these products can, to a large extent, be controlled by ensuring that the genetic sequence encoding the biopharmaceutical has been inserted stably into the host cell genome. However, the effective control of post-translational modifications such as glycosylation is much more of a challenge requiring an understanding of the cellular mechanisms that lead to different profiles along with how they can be manipulated or at least controlled by bioprocessing parameters. Yet the glycosylation profile is an important characteristic of a biopharmaceutical because of its potential to effect the biological properties of the drug such as pharmacokinetics, bioactivity and antigenicity amongst others.
Cellular Factors Impact Glycosylation
In an article entitled “Optimisationof the cellular metabolism of glycosylation for recombinant proteins producedby mammalian cell systems” (Cytotechnology, 2006, 50:57-76), Mike Butler from the University of Manitoba describes the following factors that impact glycosylation within the environment of the cell:
· 3D protein structure
· Enzyme repertoire of the host cell
· Transit time through Golgi apparatus
· Availability of intracellular sugar-nucleotide donors
7 Bioprocess Parameters For Controlling Biopharmaceutical Glycosylation
Research described in Bulter’s paper has shown that engineers can utilize a range of bioprocessing parameters to effect these intracellular factors and control glycosylation profiles such as:
2. Concentration of Ammonia
4. Dissolved oxygen levels
5. Cell line selection
6. Cell growth rates
7. Protein production rate
Modelling Glycosylation Patterns
The relationship between processing parameters and recombinant protein glycosylation patterns can be determined experimentally using scale-down models and multifactorial experimental designs. However, development costs and time would be reduced still further if models capable of predicting glycol-profiles could be developed and is now a subject of investigation by researchers around the world.
Mike Butler is scheduled topresent a talk entitled “Modeling of Glycosylation – Predicting Profiles of Glycosylation with Metabolic Data” at the Bioprocess International Conference and Exposition to be held on October 26-29, 2015 in Boston.
Join me at #BPIconf
Contact me at firstname.lastname@example.org
Dr Nick Hutchinson has a Masters and Doctorate in Biochemical Engineering from University College London, UK where he focused on laboratory tools for rapid bioprocess development and characterization. He then worked at Lonza Biologics in an R&D function investigating novel methods for large-scale antibody purification before moving to an operational role scaling-up and transferring manufacturing processes between Lonza sites in the UK, Spain and USA. Nick now works in Market Development at Parker domnick hunter where his focus is in bringing Parker's strengths in Motion & Control to Bioprocessing. This will enable customers to improve the quality and deliverability of existing and future biopharmaceuticals.
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