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Harnessing secretor...
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Malm, Magdalena,1983-KTH,Proteinteknologi
(author)
Harnessing secretory pathway differences between HEK293 and CHO to rescue production of difficult to express proteins
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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Elsevier BV,2022
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printrdacarrier
Numbers
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LIBRIS-ID:oai:DiVA.org:kth-313037
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https://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-313037URI
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https://doi.org/10.1016/j.ymben.2022.03.009DOI
Supplementary language notes
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Language:English
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Summary in:English
Part of subdatabase
Classification
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Subject category:ref swepub-contenttype
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Subject category:art swepub-publicationtype
Notes
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QC 20220531
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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.
Subject headings and genre
Added entries (persons, corporate bodies, meetings, titles ...)
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Kuo, Chih-ChungUniv 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.
(author)
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Moradi, MonaKTH,Proteinvetenskap(Swepub:kth)u1b2x5ha
(author)
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Mebrahtu, AmanKTH,Proteinvetenskap(Swepub:kth)u1l336z7
(author)
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Wistbacka, NumKTH,Proteinvetenskap(Swepub:kth)u12nfx7m
(author)
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Razavi, RoniaKTH,Proteinvetenskap(Swepub:kth)u1qhdsth
(author)
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Volk, Anna-LuisaKTH,Proteinteknologi(Swepub:kth)u1j049o2
(author)
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Lundqvist, MagnusKTH,Proteinteknologi(Swepub:kth)u1hfekeg
(author)
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Kotol, DavidKTH,Systembiologi,Science for Life Laboratory, SciLifeLab(Swepub:kth)u1yd1hdh
(author)
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Tegel, HannaKTH,Proteinvetenskap(Swepub:kth)u1nou8yx
(author)
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Hober, Sophia,Professor,1965-KTH,Proteinteknologi(Swepub:kth)u11qqzc1
(author)
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Edfors, FredrikKTH,Science for Life Laboratory, SciLifeLab,Systembiologi(Swepub:kth)u149ml0e
(author)
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Gräslund, TorbjörnKTH,Proteinvetenskap(Swepub:kth)u1dl39rj
(author)
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Chotteau, Véronique,Docent,1963-KTH,Proteinvetenskap(Swepub:kth)u1gyk88o
(author)
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Field, RayAstraZeneca, BioPharmaceut R&D, BioPharmaceut Dev, Cell Culture & Fermentat Sci, Cambridge, England.
(author)
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Varley, Paul G.AstraZeneca, BioPharmaceut R&D, BioPharmaceut Dev, Cell Culture & Fermentat Sci, Cambridge, England.
(author)
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Roth, Robert G.AstraZeneca, Discovery Biol, BioPharmaceut R&D, Discovery Sci, Gothenburg, Sweden.
(author)
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Lewis, Nathan E.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.
(author)
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Hatton, DianeAstraZeneca, BioPharmaceut R&D, BioPharmaceut Dev, Cell Culture & Fermentat Sci, Cambridge, England.
(author)
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Rockberg, JohanKTH,Proteinteknologi(Swepub:kth)u130jo0a
(author)
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KTHProteinteknologi
(creator_code:org_t)
Related titles
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In:Metabolic engineering: Elsevier BV72, s. 171-1871096-71761096-7184
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- By the author/editor
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Malm, Magdalena, ...
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Kuo, Chih-Chung
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Moradi, Mona
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Mebrahtu, Aman
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Wistbacka, Num
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Razavi, Ronia
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show more...
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Volk, Anna-Luisa
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Lundqvist, Magnu ...
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Kotol, David
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Tegel, Hanna
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Hober, Sophia, P ...
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Edfors, Fredrik
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Gräslund, Torbjö ...
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Chotteau, Véroni ...
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Field, Ray
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Varley, Paul G.
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Roth, Robert G.
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Lewis, Nathan E.
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Hatton, Diane
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Rockberg, Johan
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Genetics
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Metabolic engine ...
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Royal Institute of Technology