Xbp1-based engineering of secretory capacity enhances the productivity of Chinese hamster ovary cells

Metabolic Engineering
Marcel Tigges, Martin Fussenegger

Abstract

A variety of successful transcription and translation engineering strategies implemented during the past decade have driven the specific productivity of mammalian cells to an apparent limit. Restricted post-translation competence has since been considered the major bottleneck preventing mammalian cells from fully exploiting their physiologic production capacity in a biopharmaceutical manufacturing scenario. Through ectopic expression of the human transcription factor Xbp1 (X-box-binding-protein 1), evolved to manage plasma cell differentiation and coordinate the unfolded protein response, we have specifically expanded the endoplasmic reticulum and the Golgi of transgenic Chinese hamster ovary (CHO-K1)-derived cell lines with a resulting increase in overall production capacity. Xbp-1-based engineering of secretory bottlenecks was compatible with a variety of different promoter–product gene configurations suggesting that Xbp-1 induces generic production increases in CHO-K1 cell derivatives. Secretion engineering, illustrated here by Xbp1-based reprogramming of the post-translational processing machinery, provides a first insight into mastering a major system bottleneck which impacts biopharmaceutical manufacturing of secreted pro...Continue Reading

References

Jun 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·M Gossen, H Bujard
Jul 9, 1999·Biotechnology and Bioengineering·H KaufmannJ E Bailey
Apr 26, 2000·Proceedings of the National Academy of Sciences of the United States of America·K MoriT Yura
Dec 18, 2001·Biotechnology and Bioengineering·S SchlatterM Fussenegger
Nov 15, 2002·Biotechnology and Bioengineering·Stefan Schlatter, Martin Fussenegger
Nov 15, 2002·Biotechnology and Bioengineering·Renata E Cudna, Alan J Dickson
Feb 15, 2003·Developmental Cell·Hiderou YoshidaKazutoshi Mori
Mar 4, 2003·Nature Reviews. Molecular Cell Biology·Lars Ellgaard, Ari Helenius
Aug 6, 2003·Trends in Neurosciences·Mark S FormanJohn Q Trojanowski
Jan 20, 2004·Trends in Cell Biology·D Thomas Rutkowski, Randal J Kaufman
Mar 25, 2004·Trends in Biotechnology·Nilou Arden, Michael J Betenbaugh
Oct 7, 2004·Current Opinion in Biotechnology·Wilfried Weber, Martin Fussenegger
May 11, 2005·Biochemical and Biophysical Research Communications·Soshi KanemotoKazunori Imaizumi
Jun 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Beat P Kramer, Martin Fussenegger
Feb 14, 2006·Metabolic Engineering·Wilfried WeberMartin Fussenegger

❮ Previous
Next ❯

Citations

Sep 5, 2014·Plant Cell Reports·David Rhys Thomas, Amanda Maree Walmsley
Sep 22, 2007·Biotechnology Letters·Martin Schröder
May 8, 2009·Journal of Cell Science·Hemamalini BommiasamyJoseph W Brewer
Apr 6, 2011·The Journal of Biological Chemistry·Haruki HasegawaRandal R Ketchem
Nov 13, 2008·Cytotechnology·Darrin KuystermansMohamed Al-Rubeai
Nov 13, 2008·Cytotechnology·Saeed U Khan, Martin Schröder
Sep 13, 2013·Cytotechnology·Ahmad M HaredyTakeshi Omasa
Mar 11, 2008·Molecular Biotechnology·Mariana Campos-da-PazMarcelo Macedo Brigido
Dec 14, 2011·Applied Microbiology and Biotechnology·Jee Yon KimGyun Min Lee
Nov 3, 2015·Biotechnology Advances·Simon FischerKerstin Otte
Dec 22, 2015·Journal of Biotechnology·Aizhan TastanovaMartin Fussenegger
Feb 5, 2013·Metabolic Engineering·Jens NiklasElmar Heinzle
Mar 5, 2016·Applied Microbiology and Biotechnology·Renate Kunert, David Reinhart
Aug 26, 2014·Current Opinion in Biotechnology·Karen M Polizzi, Cleo Kontoravdi
Oct 1, 2008·Drug Discovery Today. Technologies·Mattia MatasciFlorian M Wurm
Jan 13, 2009·Journal of Bioscience and Bioengineering·Takeshi OmasaHisao Ohtake
Nov 26, 2008·Protein Expression and Purification·Sabine Geisse
May 13, 2008·Trends in Biotechnology·Dethardt MüllerJohannes Grillari
Dec 18, 2007·Current Opinion in Biotechnology·Gargi SethWei-Shou Hu
Nov 8, 2008·Biotechnology and Bioengineering·Ren-Wang Peng, Martin Fussenegger
Jan 20, 2011·Biotechnology and Bioengineering·Ren-Wang PengMartin Fussenegger
Oct 4, 2011·Biotechnology and Bioengineering·Natalia GomezInn H Yuk
Feb 26, 2013·Biotechnology and Bioengineering·Zhimei DuPranhitha Reddy
Apr 16, 2010·Biotechnology and Applied Biochemistry·Yiping LimMiranda G S Yap
Nov 26, 2009·Biotechnology Progress·Sebastian C Y KuSheng-Hao Chao
Aug 8, 2007·Trends in Biotechnology·Timothy J GriffinWei-Shou Hu
Aug 7, 2013·Biotechnology Advances·Vaibhav JadhavNicole Borth
May 15, 2015·Biotechnology Letters·Huong LeWei-Shou Hu

❮ Previous
Next ❯

Related Concepts

Related Feeds

B cells: Gene Expression

B lymphocytes are white blood cells that play a role in the adaptive immune system by secreting antibodies. Here is the latest research on gene expression in B cells.

Arterial-Venous in Development & Disease

Arterial-venous development may play a crucial role in cardiovascular diseases. Here is the latest research.

B cell Differentiation

Depending on the signal received through the B cell receptor and other receptors, B cells differentiate into follicular or marginal zone B cells. Here is the latest research pertaining to this differentiation process.