Enhancing CHO by Mammalian Systems Biotechnology (eCHO systems)

Deliverables

Documents, reports (9)

Integration of proteomic and post-translational data

Analysis of proteomic and post-translational data sets and development of cellular systems models including secretion and glycosylation.

Effects of lncRNAs

Determination of the role of long non-coding RNA in CHO and application to models.

High throughput screens for gene function and engineered CHO chassis designed for improved recombinant protein yields

Manipulation of key target genes to generate new CHO chassis validated under industrial conditions

Final Report

Final Report delivered to EC

Omics-datasets distributed

Large omics datasets published and available to the scientific community

Enhancing translational rates and protein synthesis

Establishment of CHO cell lines with enhanced translational and protein synthesis capacity

Publications

At least 2 peer reviewed publications from each ESR

Mid Term review meeting

Meeting with fellows, members of consortium and REA representative to assess the work progress and achievements

Transcriptional and genomic cross-effects

Determination of gene copy number variation/mutations and models describing transcriptional regulation and control.

Other (2)

Training complete

All NTA courses held at each hosting university partner

Appointment of SAB

Supervisory Board committee members selected

Publications

Peer reviewed articles (21)

Impact of CHO Metabolism on Cell Growth and Protein Production: An Overview of Toxic and Inhibiting Metabolites and Nutrients

Author(s): Sara Pereira, Helene Faustrup Kildegaard, Mikael Rørdam Andersen
Published in: Biotechnology Journal, 13/3, 2018, Page(s) 1700499, ISSN 1860-6768
Publisher: Wiley - VCH Verlag GmbH & CO. KGaA
DOI: 10.1002/biot.201700499

CRISPR/Cas9-multiplexed editing of Chinese hamster ovary B4Gal-T1, 2, 3 and 4 tailors N-glycan profiles of therapeutics and secreted host cell proteins

Author(s): Thomas Amann, Anders Holmgaard Hansen, Stefan Kol, Gyun Min Lee, Mikael Rørdam Andersen, Helene Faustrup Kildegaard
Published in: Biotechnology Journal, 2018, Page(s) 1800111, ISSN 1860-6768
Publisher: Wiley - VCH Verlag GmbH & CO. KGaA
DOI: 10.1002/biot.201800111

Using Titer and Titer Normalized to Confluence Are Complementary Strategies for Obtaining Chinese Hamster Ovary Cell Lines with High Volumetric Productivity of Etanercept

Author(s): Nuša Pristovšek, Henning Gram Hansen, Daria Sergeeva, Nicole Borth, Gyun Min Lee, Mikael Rørdam Andersen, Helene Faustrup Kildegaard
Published in: Biotechnology Journal, 13/3, 2018, Page(s) 1700216, ISSN 1860-6768
Publisher: Wiley - VCH Verlag GmbH & CO. KGaA
DOI: 10.1002/biot.201700216

An Online Compendium of CHO RNA-Seq Data Allows Identification of CHO Cell Line-specific Transcriptomic Signatures

Author(s): Ankita Singh, Helene F. Kildegaard, Mikael R. Andersen
Published in: Biotechnology Journal, 2018, Page(s) 1800070, ISSN 1860-6768
Publisher: Wiley - VCH Verlag GmbH & CO. KGaA
DOI: 10.1002/biot.201800070

CRISPR-Based Targeted Epigenetic Editing Enables Gene Expression Modulation of the Silenced Beta-Galactoside Alpha-2,6-Sialyltransferase 1 in CHO Cells

Author(s): Nicolas Marx, Clemens Grünwald-Gruber, Nina Bydlinski, Heena Dhiman, Ly Ngoc Nguyen, Gerald Klanert, Nicole Borth
Published in: Biotechnology Journal, 2018, Page(s) 1700217, ISSN 1860-6768
Publisher: Wiley - VCH Verlag GmbH & CO. KGaA
DOI: 10.1002/biot.201700217

Enhanced Genome Editing Tools For Multi-Gene Deletion Knock-Out Approaches Using Paired CRISPR sgRNAs in CHO Cells

Author(s): Valerie Schmieder, Nina Bydlinski, Richard Strasser, Martina Baumann, Helene Faustrup Kildegaard, Vaibhav Jadhav, Nicole Borth
Published in: Biotechnology Journal, 13/3, 2018, Page(s) 1700211, ISSN 1860-6768
Publisher: Wiley - VCH Verlag GmbH & CO. KGaA
DOI: 10.1002/biot.201700211

A reference genome of the Chinese hamster based on a hybrid assembly strategy

Author(s): Oliver Rupp, Madolyn L. MacDonald, Shangzhong Li, Heena Dhiman, Shawn Polson, Sven Griep, Kelley Heffner, Inmaculada Hernandez, Karina Brinkrolf, Vaibhav Jadhav, Mojtaba Samoudi, Haiping Hao, Brewster Kingham, Alexander Goesmann, Michael J. Betenbaugh, Nathan E. Lewis, Nicole Borth, Kelvin H. Lee
Published in: Biotechnology and Bioengineering, 2018, ISSN 0006-3592
Publisher: Wiley - V C H Verlag GmbbH & Co.
DOI: 10.1002/bit.26722

The Long Non-Coding RNA Transcriptome Landscape in CHO Cells Under Batch and Fed-Batch Conditions

Author(s): Davide Vito, Christopher Mark Smales
Published in: Biotechnology Journal, 2018, Page(s) 1800122, ISSN 1860-6768
Publisher: Wiley - VCH Verlag GmbH & CO. KGaA
DOI: 10.1002/biot.201800122

Exploring the Potential Application of Short Non-Coding RNA-Based Genetic Circuits in Chinese Hamster Ovary Cells

Author(s): Ricardo Valdés-Bango Curell, Niall Barron
Published in: Biotechnology Journal, 2018, Page(s) 1700220, ISSN 1860-6768
Publisher: Wiley - VCH Verlag GmbH & CO. KGaA
DOI: 10.1002/biot.201700220

Meta-Analysis of Publicly Available Chinese Hamster Ovary (CHO) Cell Transcriptomic Datasets for Identifying Engineering Targets to Enhance Recombinant Protein Yields

Author(s): Linas Tamošaitis, Christopher Mark Smales
Published in: Biotechnology Journal, 2018, Page(s) 1800066, ISSN 1860-6768
Publisher: Wiley - VCH Verlag GmbH & CO. KGaA
DOI: 10.1002/biot.201800066

Glyco-engineered CHO cell lines producing alpha-1-antitrypsin and C1 esterase inhibitor with fully humanized N-glycosylation profiles

Author(s): Thomas Amann, Anders Holmgaard Hansen, Stefan Kol, Henning Gram Hansen, Johnny Arnsdorf, Saranya Nallapareddy, Bjørn Voldborg, Gyun Min Lee, Mikael Rørdam Andersen, Helene Faustrup Kildegaard
Published in: Metabolic Engineering, 52, 2019, Page(s) 143-152, ISSN 1096-7176
Publisher: Academic Press
DOI: 10.1016/j.ymben.2018.11.014

Engineering of the cellular translational machinery and non-coding RNAs to enhance CHO cell growth, recombinant product yields and quality

Author(s): Davide Vito, C Mark Smales
Published in: Current Opinion in Chemical Engineering, 22, 2018, Page(s) 199-208, ISSN 2211-3398
Publisher: Elsevier BV
DOI: 10.1016/j.coche.2018.11.002

Application of a curated genome-scale metabolic model of CHO DG44 to an industrial fed-batch process

Author(s): Cyrielle Calmels, Andréa McCann, Laetitia Malphettes, Mikael Rørdam Andersen
Published in: Metabolic Engineering, 51, 2019, Page(s) 9-19, ISSN 1096-7176
Publisher: Academic Press
DOI: 10.1016/j.ymben.2018.09.009

The Expression Pattern of the Phosphoproteome Is Significantly Changed During the Growth Phases of Recombinant CHO Cell Culture

Author(s): Prashant Kaushik, Michael Henry, Martin Clynes, Paula Meleady
Published in: Biotechnology Journal, 13/10, 2018, Page(s) 1700221, ISSN 1860-6768
Publisher: Wiley - VCH Verlag GmbH & CO. KGaA
DOI: 10.1002/biot.201700221

Differential Phosphoproteomic Analysis of Recombinant Chinese Hamster Ovary Cells Following Temperature Shift

Author(s): Michael Henry, Martin Power, Prashant Kaushik, Orla Coleman, Martin Clynes, Paula Meleady
Published in: Journal of Proteome Research, 16/7, 2017, Page(s) 2339-2358, ISSN 1535-3893
Publisher: American Chemical Society
DOI: 10.1021/acs.jproteome.6b00868

Epigenetic regulation of gene expression in Chinese Hamster Ovary cells in response to the changing environment of a batch culture

Author(s): Inmaculada Hernandez, Heena Dhiman, Gerald Klanert, Vaibhav Jadhav, Norbert Auer, Michael Hanscho, Martina Baumann, Anna Esteve-Codina, Marc Dabad, Jessica Gómez, Tyler Alioto, Angelika Merkel, Emanuele Raineri, Simon Heath, Daniel Rico, Nicole Borth
Published in: Biotechnology and Bioengineering, 116/3, 2019, Page(s) 677-692, ISSN 0006-3592
Publisher: Wiley - V C H Verlag GmbbH & Co.
DOI: 10.1002/bit.26891

RTN3 Is a Novel Cold-Induced Protein and Mediates Neuroprotective Effects of RBM3

Author(s): Amandine Bastide, Diego Peretti, John R.P. Knight, Stefano Grosso, Ruth V. Spriggs, Xavier Pichon, Thomas Sbarrato, Anne Roobol, Jo Roobol, Davide Vito, Martin Bushell, Tobias von der Haar, C. Mark Smales, Giovanna R. Mallucci, Anne E. Willis
Published in: Current Biology, 2017, ISSN 0960-9822
Publisher: Cell Press
DOI: 10.1016/j.cub.2017.01.047

Improving the secretory capacity of Chinese hamster ovary cells by ectopic expression of effector genes: Lessons learned and future directions

Author(s): Henning Gram Hansen, Nuša Pristovšek, Helene Faustrup Kildegaard, Gyun Min Lee
Published in: Biotechnology Advances, 35/1, 2017, Page(s) 64-76, ISSN 0734-9750
Publisher: Elsevier BV
DOI: 10.1016/j.biotechadv.2016.11.008

Ultra-deep next generation mitochondrial genome sequencing reveals widespread heteroplasmy in Chinese hamster ovary cells

Author(s): Paul S. Kelly, Colin Clarke, Alan Costello, Craig Monger, Justine Meiller, Heena Dhiman, Nicole Borth, Michael J. Betenbaugh, Martin Clynes, Niall Barron
Published in: Metabolic Engineering, 2017, ISSN 1096-7176
Publisher: Academic Press
DOI: 10.1016/j.ymben.2017.02.001

Genetic and epigenetic variation across genes involved in energy metabolism and mitochondria of Chinese Hamster Ovary cell lines

Author(s): Heena Dhiman, Matthias P. Gerstl, David Ruckerbauer, Michael Hanscho, Heinz Himmelbauer, Colin Clarke, Niall Barron, Jürgen Zanghellini, Nicole Borth
Published in: Biotechnology Journal, 2019, Page(s) 1800681, ISSN 1860-6768
Publisher: Wiley - VCH Verlag GmbH & CO. KGaA
DOI: 10.1002/biot.201800681

Systematic Evaluation of Site-Specific Recombinant Gene Expression for Programmable Mammalian Cell Engineering

Author(s): Nuša Pristovšek, Saranya Nallapareddy, Lise Marie Grav, Hooman Hefzi, Nathan E. Lewis, Peter Rugbjerg, Henning Gram Hansen, Gyun Min Lee, Mikael Rørdam Andersen, Helene Faustrup Kildegaard
Published in: ACS Synthetic Biology, 8/4, 2019, Page(s) 758-774, ISSN 2161-5063
Publisher: American Chemical Society
DOI: 10.1021/acssynbio.8b00453

Book chapters (2)

A Bioinformatics Pipeline for the Identification of CHO Cell Differential Gene Expression from RNA-Seq Data

Author(s): Craig Monger, Krishna Motheramgari, John McSharry, Niall Barron, Colin Clarke
Published in: Heterologous Protein Production in CHO Cells, 1603, 2017, Page(s) 169-186, ISBN 978-1-4939-6971-5
Publisher: Springer New York
DOI: 10.1007/978-1-4939-6972-2_11

Phosphopeptide Enrichment and LC-MS/MS Analysis to Study the Phosphoproteome of Recombinant Chinese Hamster Ovary Cells

Author(s): Michael Henry, Orla Coleman, Prashant, Martin Clynes, Paula Meleady
Published in: Heterologous Protein Production in CHO Cells, 1603, 2017, Page(s) 195-208, ISBN 978-1-4939-6971-5
Publisher: Springer New York
DOI: 10.1007/978-1-4939-6972-2_13