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Biomedical Engineering and Bioengineering Commons™
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Articles 1 - 7 of 7
Full-Text Articles in Biomedical Engineering and Bioengineering
Targeting Product Quality: Where Systems Biotechnology And Process Design Meet, Markus Michael Muller, Jan Bechmann, Ingo Gorr, Harald Bradl, Jan Visser
Targeting Product Quality: Where Systems Biotechnology And Process Design Meet, Markus Michael Muller, Jan Bechmann, Ingo Gorr, Harald Bradl, Jan Visser
Cell Culture Engineering XV
Product quality is a result of the entire production process including protein sequence, host cell, media and process parameters. Many of the desired product properties are defined by posttranslational modifications with impact on biological activity, immunogenicity, half-life or stability. In‑depth understanding of the host cells capabilities as well as of the process interactions enables the targeted modulation of product quality attributes by rational selection of host cells and design of bioprocesses. This is valuable for new biological molecules in order to improve efficacy, reduce side effects, access new patient populations. For biosimilars this allows developing into defined quality attribute profiles. …
Understanding And Controlling Sialyation In A Cho Fusion Protein At Lab And Manufacturing Scale Using Targeted Omics Techniques, Amanda Lewis, Nelly Aranibar, William Croughan, Nicholas Abu-Absi, Bethanne Warrack, Michael Borys, Michael Reily, Zheng Jian Li
Understanding And Controlling Sialyation In A Cho Fusion Protein At Lab And Manufacturing Scale Using Targeted Omics Techniques, Amanda Lewis, Nelly Aranibar, William Croughan, Nicholas Abu-Absi, Bethanne Warrack, Michael Borys, Michael Reily, Zheng Jian Li
Cell Culture Engineering XV
Biologics, including antibodies, hormones and cytokines, represent an increasingly important class of therapeutics, with 7 of the 10 top selling drugs from 2013 in this class. The glycosylation distribution of these proteins is an important characteristic that can impact biological activity, circulatory half-life, and immunogenicity. One property that affects glycoproteins is the terminal addition of N-acetylneuraminic acid (sialic acid) to glycosylation chains. Despite the importance of glycosylation in many therapeutic proteins, limited information is available to date linking process parameters to changes in glycosylation distribution. The majority of the work that has been done is limited to a small number …
A Stochastic Model To Study Genetic And Metabolic Effects On N-Linked Protein Glycosylation, Phillip Spahn, Anders Hansen, Henning Hansen, Johnny Arnsdorf, Helene Kildegaard, Nathan Lewis
A Stochastic Model To Study Genetic And Metabolic Effects On N-Linked Protein Glycosylation, Phillip Spahn, Anders Hansen, Henning Hansen, Johnny Arnsdorf, Helene Kildegaard, Nathan Lewis
Cell Culture Engineering XV
Glycosylation is a vital processing step for a large number of cellular proteins as it critically affects protein stability and solubility as well as protein-protein interactions. As a consequence, glycosylation is a major quality attribute of recombinant proteins in biopharmaceutical applications. However, since glycosylation does not follow a template, but instead involves a complex interplay of various influencing factors in the Golgi, tailoring glycosylation towards certain desired attributes is challenging and usually requires trial-and-error experimentation. Computational modeling offers an intriguing option to understand and rationally engineer the complex reaction network underlying glycosylation. Here we present a computational model that describes …
Cho-Specific Recombinant Protein Glycosylation Reaction Network, Benjamin Kremkow, Kelvin Lee
Cho-Specific Recombinant Protein Glycosylation Reaction Network, Benjamin Kremkow, Kelvin Lee
Cell Culture Engineering XV
Protein glycosylation is one of the most important product quality attributes and impacts efficacy, half-life, and immunogenicity. Previous glycosylation models effectively simulated the key parts of the N-glycosylation pathway. Building upon these prior efforts as well as recent CHO-K1 and Chinese hamster (CH) genome sequencing efforts, we share a new model for CHO- and CH- glycosylation. The model contains all N-glycosylation-related genes and all of the metabolic genes associated with central carbon metabolism, nucleotide sugar precursor synthesis, and nucleotide sugar transport annotated from the CHO-K1 and CH genomes. The model predicts both intracellular and secreted glycans for both mAb and …
Controller Design For Effective Glycosylation Control In Mabs, Devesh Radhakrishnan
Controller Design For Effective Glycosylation Control In Mabs, Devesh Radhakrishnan
Cell Culture Engineering XV
Monoclonal antibodies (mAbs), a class of commercially viable biotherapeutics, undergo post-translational modifications when expressed in mammalian cell lines, resulting in structural and pharmacological changes in the protein. One such post translational modification is N-linked glycosylation, where the non-template driven enzymatic attachment of different sugar moieties (glycans) to the mAb can alter the product quality of the mAb, compromising the efficacy and safety of the drug product. While significant research effort has been devoted to developing techniques for characterizing and monitoring the glycosylation pattern in mAbs, a robust technique for controlling the glycan distribution and ensuring consistent glycosylation does not currently …
Predictive Engineering Of Cho Cells Using Systems Biology Models, Nathan Lewis
Predictive Engineering Of Cho Cells Using Systems Biology Models, Nathan Lewis
Cell Culture Engineering XV
Decades of bioprocess optimization have resulted in substantial improvements in recombinant protein production. However, some proteins remain difficult to express, and there is an increasing awareness of the need for improved control of critical quality attributes of recombinant protein drugs. To enable cell engineering efforts to enhance protein production and control product quality, we have enumerated the CHO cell parts through genome sequencing efforts,1,2 and are now providing context to these parts by reconstructing genome-scale networks of the secretory pathway, glycosylation, and metabolism CHO (Figure 1). Using these models, which account for the activities of more than 2000 genes, …
Targeted Integration Of Multiple Active Sites In Cho Genome For Rapid Generation Of Stable And High Monoclonal Antibody Producing Cell Lines, Yuansheng Yang
Targeted Integration Of Multiple Active Sites In Cho Genome For Rapid Generation Of Stable And High Monoclonal Antibody Producing Cell Lines, Yuansheng Yang
Cell Culture Engineering XV
Mammalian cell lines used for manufacturing recombinant therapeutic proteins need to have high productivity, long term stable production and good product quality. The process of cell line development currently used in industry is based on random integration of the plasmid vectors into genome. Due to clonal variation, hundreds to thousands of clones are screened through multiple stages of evaluation. The whole process takes at least a few months and is extremely tedious. Targeted integration-based cell line development is attractive as the plasmid vectors integrate into predetermined active sites in genomes. All targeted cell lines have same genetic background and thus …