Open this publication in new window or tab >>KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Technology.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Technology.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology. KTH, Centres, Science for Life Laboratory, SciLifeLab.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Technology.
KTH, Centres, Science for Life Laboratory, SciLifeLab. KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Systems Biology.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Engineering.
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science.
AstraZeneca, BioPharmaceut R&D, BioPharmaceut Dev, Cell Culture & Fermentat Sci, Cambridge, England..
AstraZeneca, BioPharmaceut R&D, BioPharmaceut Dev, Cell Culture & Fermentat Sci, Cambridge, England..
AstraZeneca, Discovery Biol, BioPharmaceut R&D, Discovery Sci, Gothenburg, Sweden..
Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA.;Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA.;Univ Calif San Diego, Novo Nordisk Fdn Ctr Biosustainabil, San Diego, CA 92093 USA..
AstraZeneca, BioPharmaceut R&D, BioPharmaceut Dev, Cell Culture & Fermentat Sci, Cambridge, England..
KTH, School of Engineering Sciences in Chemistry, Biotechnology and Health (CBH), Protein Science, Protein Technology.
Show others...
2022 (English)In: Metabolic engineering, ISSN 1096-7176, E-ISSN 1096-7184, Vol. 72, p. 171-187Article in journal (Refereed) Published
Abstract [en]
Biologics represent the fastest growing group of therapeutics, but many advanced recombinant protein moieties remain difficult to produce. Here, we identify metabolic engineering targets limiting expression of recombinant human proteins through a systems biology analysis of the transcriptomes of CHO and HEK293 during recombinant expression. In an expression comparison of 24 difficult to express proteins, one third of the challenging human proteins displayed improved secretion upon host cell swapping from CHO to HEK293. Guided by a comprehensive transcriptomics comparison between cell lines, especially highlighting differences in secretory pathway utilization, a co-expression screening of 21 secretory pathway components validated ATF4, SRP9, JUN, PDIA3 and HSPA8 as productivity boosters in CHO. Moreover, more heavily glycosylated products benefitted more from the elevated activities of the N- and O-glycosyltransferases found in HEK293. Collectively, our results demonstrate the utilization of HEK293 for expression rescue of human proteins and suggest a methodology for identification of secretory pathway components for metabolic engineering of HEK293 and CHO.
Place, publisher, year, edition, pages
Elsevier BV, 2022
Keywords
HEK293, CHO, Bioproduction, Protein secretion, Transcriptomics, Differential gene expression analysis, Secretory pathway
National Category
Genetics and Genomics
Identifiers
urn:nbn:se:kth:diva-313037 (URN)10.1016/j.ymben.2022.03.009 (DOI)000793760100001 ()35301123 (PubMedID)2-s2.0-85126895070 (Scopus ID)
Note
QC 20220531
2022-05-312022-05-312025-02-07Bibliographically approved