High-throughput profiling of nucleotides and nucleotide sugars to evaluate their impact on antibody N-glycosylation

Villiger, Thomas K.; Steinhoff, Robert; Ivarsson, Mattias E.; Solacroup, Thomas; Stettler, Matthieu; Broly, Hervé; Krismer, Jasmin; Pabst, Martin; Zenobi, Renato; Morbidelli, Massimo; Šoóš, Miroslav

doi:10.1016/j.jbiotec.2016.04.039

Cited by 38 publications

(25 citation statements)

References 43 publications

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“…The various types of multi‐omics and systems metabolic models, as well as approaches that focus on combining genomics and proteomics with glycomics have been used to identify pathways that could potentially aid in either the development of media and feeds, or engineer CHO cells in order to increase productivity or product consistency for bioproduction . Baycin‐Hizal et al mapped proteomic data to CHO genomic and transcriptomic data to identify over 6000 proteins.…”

Section: Conclusion: Multi‐omics and Systems Approachesmentioning

confidence: 99%

CHO‐Omics Review: The Impact of Current and Emerging Technologies on Chinese Hamster Ovary Based Bioproduction

Stolfa

Smonskey

Boniface

et al. 2017

Biotechnology Journal

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CHO cells are the most prevalent platform for modern bio-therapeutic production. Currently, there are several CHO cell lines used in bioproduction with distinct characteristics and unique genotypes and phenotypes. These differences limit advances in productivity and quality that can be achieved by the most common approaches to bioprocess optimization and cell line engineering. Incorporating omics-based approaches into current bioproduction processes will complement traditional methodologies to maximize gains from CHO engineering and bioprocess improvements. In order to highlight the utility of omics technologies in CHO bioproduction, the authors discuss current applications as well as limitations of genomics, transcriptomics, proteomics, metabolomics, lipidomics, fluxomics, glycomics, and multi-omics approaches and the potential they hold for the future of bioproduction. Multiple omics approaches are currently being used to improve CHO bioprocesses; however, the application of these technologies is still limited. As more CHO-omic datasets become available and integrated into systems models, the authors expect significant gains in product yield and quality. While individual omics technologies provide incremental improvements in bioproduction, the authors will likely see the most significant gains by applying multi-omics and systems biology approaches to individual CHO cell lines.

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Section: Conclusion: Multi‐omics and Systems Approachesmentioning

confidence: 99%

CHO‐Omics Review: The Impact of Current and Emerging Technologies on Chinese Hamster Ovary Based Bioproduction

Stolfa

Smonskey

Boniface

et al. 2017

Biotechnology Journal

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“…Among all the nucleotide sugar donors, availability of UDP-Gal is reported to be the most limiting 88 , and supplementation of culture with uridine and galactose can increase intracellular UDP-Gal levels. Mn 2+ is required for the activity of galactosyltransferase, and is supplemented if its availability in the medium is limiting or if the culture results in reduced intracellular Mn 2+ (ref.…”

Section: Advances In Controlling Glycoform Profile Of Glycoproteinsmentioning

confidence: 99%

Cell Culture Processes for Biopharmaceutical Manufacturing

Gadgil

2017

Current Science

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Recombinant proteins manufactured using animal cell culture processes comprise a significant fraction of biopharmaceuticals. With the expiry of patents on this class of therapeutics, there is also a significant interest in manufacture of biosimilar versions of such therapeutics. This article provides a birds-eye view of upstream process development for animal cell culture processes, with a focus on advances pertinent to the development of processes for biosimilars.

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“…In the last decade, several trends could be observed in biopharmaceutical process development: a shift from yield maximization to quality optimization, the utilization of miniaturized and parallelized high throughput techniques, single‐use technologies, continuous bioprocessing, and continuous data acquisition as well as the utilization of data‐ and knowledge‐driven tools for process analysis, forecasting, monitoring, and control . Many of these trends are already well‐established in the “older” industries such as automotive.…”

Section: Introductionmentioning

confidence: 99%

“…In the last decade, titers in mammalian cell cultures could be increased to values as high as 5 g L −1 in production, so that the identification and modulation of the critical quality attributes (CQAs) of the product became increasingly important . The quality fingerprint of therapeutic proteins is quite complex and includes versatile biological patterns such as the glycosylation and charge variant profiles as well as the aggregated and low molecular weight forms, all of which are highly important for the efficacy, potency and safety of the drug .…”

Section: Introductionmentioning

confidence: 99%

Sequential Multivariate Cell Culture Modeling at Multiple Scales Supports Systematic Shaping of a Monoclonal Antibody Toward a Quality Target

Sokolov

Morbidelli

Butté

et al. 2018

Biotechnology Journal

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The development of cell culture processes is highly complex and requires a large number of experiments on various scales to define the design space of the final process and fulfil the regulatory requirements. This work follows an almost complete process development cycle for a biosimilar monoclonal antibody, from high throughput screening and optimization to scale-up and process validation. The key goal of this analysis is to apply tailored multivariate tools to support decision-making at every stage of process development. A toolset mainly based on Principal Component Analysis, Decision Trees, and Partial Least Square Regression combined with a Genetic Algorithm is presented. It enables to visualize the sequential improvement of the high-dimensional quality profile towards the target, provides a solid basis for the selection of effective process variables and allows to dynamically predict the complete set of product quality attributes. Additionally, this work shows the deep level of process knowledge which can be deduced from small scale experiments through such multivariate tools. The presented methodologies are generally applicable across various processes and substantially reduce the complexity, experimental effort as well as the costs and time of process development.

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High-throughput profiling of nucleotides and nucleotide sugars to evaluate their impact on antibody N-glycosylation

Cited by 38 publications

References 43 publications

CHO‐Omics Review: The Impact of Current and Emerging Technologies on Chinese Hamster Ovary Based Bioproduction

CHO‐Omics Review: The Impact of Current and Emerging Technologies on Chinese Hamster Ovary Based Bioproduction

Cell Culture Processes for Biopharmaceutical Manufacturing

Sequential Multivariate Cell Culture Modeling at Multiple Scales Supports Systematic Shaping of a Monoclonal Antibody Toward a Quality Target

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