64 results found
Cardenas-Fernandez M, Bawn M, Hamley-Bennett C, et al., 2017, An integrated biorefinery concept for conversion of sugar beet pulp into value-added chemicals and pharmaceutical intermediates, FARADAY DISCUSSIONS, Vol: 202, Pages: 415-431, ISSN: 1359-6640
Goers L, Ainsworth C, Goey CH, et al., 2017, Whole-cell Escherichia coli lactate biosensor for monitoring mammalian cell cultures during biopharmaceutical production, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 114, Pages: 1290-1300, ISSN: 0006-3592
Cover Legend The cover image, by Lisa Goers et al., is based on the Article Whole-cell Escherichia coli lactate biosensor for monitoring mammalian cell cultures during biopharmaceutical production, DOI: 10.1002/bit.26254.
Goey CH, Tsang JMH, Bell D, et al., 2017, Cascading effect in bioprocessing-The impact of mild hypothermia on CHO cell behavior and host cell protein composition., Biotechnol Bioeng
A major challenge in downstream purification of monoclonal antibodies (mAb) is the removal of host cell proteins (HCPs). Previous studies have shown that cell culture conditions significantly impact the HCP content at harvest. However, it is currently unclear how process conditions affect physiological changes in the host cell population, and how these changes, in turn, cascade down to change the HCP profile. We examined how temperature downshift (TDS) to mild hypothermia affects key upstream performance indicators, that is antibody titre, HCP concentration and HCP species, across the cell culture decline phase and at harvest through the lens of changes in cellular behavior. Mild hypothermic conditions introduced on day 5 of fed-batch Chinese hamster ovary (CHO) cell bioreactors resulted in a lower cell proliferation rate but larger percentages of healthier cells across the cell culture decline phase compared to bioreactors maintained at standard physiological temperature. Moreover, the onset of apoptosis was less evident in mild hypothermic cultures. Consequently, mild hypothermic cultures took an extra 5 days to reach an integral viable cell concentration (IVCC) and antibody yield similar to that of the control at standard physiological temperature. When cell viability dropped below 80%, mild hypothermic cell cultures had a reduced variety of HCP species by 36%, including approximately 44% and 27% lower proteases and chaperones, respectively, despite having similar HCP concentration. This study suggests that TDS may be a good strategy to provide cleaner downstream feedstocks by reducing the variety of HCPs and to maintain product integrity by reducing the number of proteases and chaperones.
Sou SN, Jedrzejewski PM, Lee K, et al., 2017, Model-based investigation of intracellular processes determining antibody Fc-glycosylation under mild hypothermia, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 114, Pages: 1570-1582, ISSN: 0006-3592
Sou SN, Lee K, Nayyar K, et al., 2017, Exploring cellular behaviour under transient gene expression and its impact on mAb productivity and Fc-glycosylation., Biotechnol Bioeng
Transient gene expression (TGE) is a methodology employed in bioprocessing for the fast provision of recombinant protein material. Mild hypothermia is often introduced to overcome the low yield typically achieved with TGE and improve specific protein productivity. It is therefore of interest to examine the impact of mild hypothermic temperatures on both the yield and quality of transiently-expressed proteins and the relationship to changes in cellular processes and metabolism. In this study, we focus on the ability of a Chinese hamster ovary cell line to galactosylate a recombinant monoclonal antibody (mAb) product. Through experimentation and flux balance analysis, our results show that TGE in mild hypothermic conditions led to a 76% increase in qP compared to TGE at 36.5(°) C in our system. This increase is accompanied by increased consumption of nutrients and amino acids, together with increased production of intracellular nucleotide sugar species and higher rates of mAb galactosylation, despite a reduced rate of cell growth. The reduction in biomass accumulation allowed cells to redistribute their energy and resources towards mAb synthesis and Fc-glycosylation. Interestingly, the higher capacity of cells to galactosylate the recombinant product in TGE at 32°C appears not to have been assisted by the upregulation of galactosyltransferases (GalTs), but by the increased expression of N-acetylglucosaminyltransferase II (GnTII) in this cell line, which facilitated the production of bi-antennary glycan structures for further processing. This article is protected by copyright. All rights reserved.
Klymenko OV, Shah N, Kontoravdi C, et al., 2016, Designing an Artificial Golgi Reactor to Achieve Targeted Glycosylation of Monoclonal Antibodies, AICHE JOURNAL, Vol: 62, Pages: 2959-2973, ISSN: 0001-1541
Niu H, Shah N, Kontoravdi C, 2016, Modelling of amorphous cellulose depolymerisation by cellulases, parametric studies and optimisation, BIOCHEMICAL ENGINEERING JOURNAL, Vol: 105, Pages: 455-472, ISSN: 1369-703X
del Val IJ, Polizzi KM, Kontoravdi C, 2016, A theoretical estimate for nucleotide sugar demand towards Chinese Hamster Ovary cellular glycosylation, SCIENTIFIC REPORTS, Vol: 6, ISSN: 2045-2322
Fan Y, Del Val IJ, Mueller C, et al., 2015, Amino Acid and Glucose Metabolism in Fed-Batch CHO Cell Culture Affects Antibody Production and Glycosylation, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 112, Pages: 521-535, ISSN: 0006-3592
Fan Y, Del Val IJ, Muller C, et al., 2015, A multi-pronged investigation into the effect of glucose starvation and culture duration on fed-batch CHO cell culture, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 112, Pages: 2172-2184, ISSN: 0006-3592
Niv H, Leak D, Shah N, et al., 2015, Metabolic characterization and modeling of fermentation process of an engineered Geobacillus thermoglucosidasius strain for bioethanol production with gas stripping, CHEMICAL ENGINEERING SCIENCE, Vol: 122, Pages: 138-149, ISSN: 0009-2509
Polizzi KM, Kontoravdi C, 2015, Genetically-encoded biosensors for monitoring cellular stress in bioprocessing, CURRENT OPINION IN BIOTECHNOLOGY, Vol: 31, Pages: 50-56, ISSN: 0958-1669
Sou SN, Sellick C, Lee K, et al., 2015, How does mild hypothermia affect monoclonal antibody glycosylation?, Biotechnology and Bioengineering, Vol: 112, Pages: 1165-1176, ISSN: 1097-0290
Jedrzejewski PM, del Val IJ, Constantinou A, et al., 2014, Towards Controlling the Glycoform: A Model Framework Linking Extracellular Metabolites to Antibody Glycosylation, INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, Vol: 15, Pages: 4492-4522, ISSN: 1422-0067
Kyriakopoulos S, Kontoravdi C, 2014, A Framework for the Systematic Design of Fed-Batch Strategies in Mammalian Cell Culture, BIOTECHNOLOGY AND BIOENGINEERING, Vol: 111, Pages: 2466-2476, ISSN: 0006-3592
Kyriakopoulos S, Kontoravdi C, 2014, Insights on biomarkers from Chinese hamster ovary ‘omics’ studies, Pharmaceutical Bioprocessing, Vol: 2, Pages: 389-401, ISSN: 2048-9145
Todri E, Amenaghawon AN, del Val IJ, et al., 2014, Global sensitivity analysis and meta-modeling of an ethanol production process, CHEMICAL ENGINEERING SCIENCE, Vol: 114, Pages: 114-127, ISSN: 0009-2509
Chen N, Bennett MH, Kontoravdi C, 2013, Analysis of Chinese hamster ovary cell metabolism through a combined computational and experimental approach, Cytotechnology, Vol: Online First
Jedrzejewski PM, Jimenez del Val I, Polizzi KM, et al., 2013, Applying quality by design to glycoprotein therapeutics: experimental and computational efforts of process control, Pharmaceutical Bioprocessing, Vol: 1, Pages: 51-69
Jimenez Del Val I, Constantinou A, Dell A, et al., 2013, An integrated mechanistic model for nucleotide sugar metabolism and monoclonal antibody glycosylation, Pages: 658-659
Jimenez del Val I, Constantinou A, Dell A, et al., 2013, A quantitative and mechanistic model for monoclonal antibody glycosylation as a function of nutrient availability during cell culture, 23rd European Society for Animal Cell Technology (ESACT) Meeting: Better Cells for Better Health
Kontoravdi C, 2013, Systematic methodology for the development of mathematical models for biological processes., Methods Mol Biol, Vol: 1073, Pages: 177-190
Synthetic biology gives researchers the opportunity to rationally (re-)design cellular activities to achieve a desired function. The design of networks of pathways towards accomplishing this calls for the application of engineering principles, often using model-based tools. Success heavily depends on model reliability. Herein, we present a systematic methodology for developing predictive models comprising model formulation considerations, global sensitivity analysis, model reduction (for highly complex models or where experimental data are limited), optimal experimental design for parameter estimation, and predictive capability checking. Its efficacy and validity are demonstrated using an example from bioprocessing. This approach systematizes the process of developing reliable mathematical models at a minimum experimental cost, enabling in silico simulation and optimization.
Kontoravdi C, Samsatli NJ, Shah N, 2013, Development and design of bio-pharmaceutical processes, CURRENT OPINION IN CHEMICAL ENGINEERING, Vol: 2, Pages: 435-441, ISSN: 2211-3398
Kyriakopoulos S, Polizzi KM, Kontoravdi C, 2013, Comparative analysis of amino acid metabolism and transport in CHO variants with different levels of productivity, JOURNAL OF BIOTECHNOLOGY, Vol: 168, Pages: 543-551, ISSN: 0168-1656
Kyriakopoulos S, Polizzi KM, Kontoravdi C, 2013, Dynamic profiling of amino acid transport and metabolism in Chinese hamster ovary cell culture., Pages: P97-P97, ISSN: 1753-6561
Polizzi KM, Hallett JP, Kontoravdi C, et al., 2013, Frontier manufacturing: Scaling up synthetic biology
Royle K, Jimenez Del Val I, Miller A, et al., 2013, Designing a synthetic Golgi reactor, Pages: 341-342
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