Engineering of chaperone systems and of the unfolded protein response

Khan, Saeed Uz Zaman; Schröder, Martin

doi:10.1007/s10616-008-9157-9

Cited by 37 publications

(18 citation statements)

References 171 publications

(244 reference statements)

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“…For instance, the specific production rate of recombinant cell lines reaches around 50 pg/cell/day (Butler and MenesesAcosta 2012), or around 90 pg/cell/day (Kober et al 2013). However, a plasma cell can secrete several thousands of immunoglobulin M molecules (Randall et al 1992), indicating that a 2.5-12-fold increase in specific productivity is possible (Khan and Schroder 2008).…”

Section: Introductionmentioning

confidence: 99%

Improved antibody production in Chinese hamster ovary cells by ATF4 overexpression

et al. 2013

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To improve antibody production in Chinese hamster ovary (CHO) cells, the humanized antibody-producing CHO DP-12-SF cell line was transfected with the gene encoding activating transcription factor 4 (ATF4), a central factor in the unfolded protein response. Overexpression of ATF4 significantly enhanced the production of antibody in the CHO DP-12-SF cell line. The specific IgG production rate of in the ATF4-overexpressing CHO-ATF4-16 cells was approximately 2.4 times that of the parental host cell line. Clone CHO-ATF4-16 did not show any change in growth rate compared with the parental cells or mock-transfected CHO-DP12-SF cells. The expression levels of mRNAs encoding both the antibody heavy and light chains in the CHO-ATF4-16 clone were analyzed. This analysis showed that ATF4 overexpression improved the total production and specific production rate of antibody without affecting the mRNA transcription level. These results indicate that ATF4 overexpression is a promising method for improving recombinant IgG production in CHO cells.

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Section: Introductionmentioning

confidence: 99%

Improved antibody production in Chinese hamster ovary cells by ATF4 overexpression

et al. 2013

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“…Many factors that enhance the production of recombinant proteins have been found (Khan and Schroder, 2008;Ku et al, 2009;van Anken and Braakman, 2005). FACS is quite useful for the high-throughput selection, cell screening and isolation methods; moreover, the combination of FACS with the coexpression of other factors (chaperones, subunits, cofactors, transcriptional regulators) facilitates the efficient and time-saving screening of effective factors along with the rapid isolation of cell populations producing high levels of recombinant proteins.…”

Section: Discussionmentioning

confidence: 99%

New strategy for rapid isolation of stable cell lines from DNA-transformed insect cells using fluorescence activated cell-sorting

Kato

Yoshizuka

Park

2010

Journal of Biotechnology

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A stably transformed insect cell expression system is superior to a baculovirus expression system, since the expression system is sustained and there is no cell lysis, but the isolation of cell lines producing recombinant proteins is time-consuming and laborious. In this study, we developed a technique for the rapid isolation and efficient cultivation of sorted cells in a 24 well deep plate Bioshaker, utilizing the fluorescence activated cell-sorting (FACS) method. TnpXme11 cells, which stably expressed GFP(uv)-beta1,3-N-acetylglucosaminyltransferase2 (GGT2), were transfected with a plasmid vector for the expression of a molecular chaperone (TnpXme11-hCNX6 cell line). The expression levels of GGT2 and the molecular chaperone fused with HcRed were analyzed by FACS. Two cell lines were established by single and double sorting. Sorting of the top 10% of the TnpXme11-hCNX6 cell population with the highest fluorescence yielded the TnpXme11-hCNX6-1 cell line. TnpXme11-hCNX6-2 cells were created in a similar fashion, as mentioned above, by a second sorting of the top 10% of the TnpXme11-hCNX6-1 cell population with the highest fluorescence. The cells thus isolated produced approximately 2-fold higher extracellular activity than that before cell sorting. This procedure can be accomplished in only 2 weeks, including transfection, isolation and analysis of high protein-producing cells, and is a breakthrough strategy for the rapid isolation of a recombinant, stable insect cell line.

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“…Such complexity was further illustrated by the drastically different capabilities of two host cell lines to express two antibody molecules at high levels even though they both expressed another antibody equally well . It is thus not surprising that reports of genetic manipulation of genes involved in the secretory pathways, such as BiP, PDI, or transcription factor Xbp-1 did not give consistent results Borth et al (2005), and reviewed by Khan and Schröder (2008).…”

Section: Host Cells and Engineering Host Cellsmentioning

confidence: 99%

Cell line development for biomanufacturing processes: recent advances and an outlook

et al. 2015

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At the core of a biomanufacturing process for recombinant proteins is the production cell line. It influences the productivity and product quality. Its characteristics also dictate process development, as the process is optimized to complement the producing cell to achieve the target productivity and quality. Advances in the past decade, from vector design to cell line screening, have greatly expanded our capability to attain producing cell lines with certain desired traits. Increasing availability of genomic and transcriptomic resources for industrially important cell lines coupled with advances in genome editing technology have opened new avenues for cell line development. These developments are poised to help biosimilar manufacturing, which requires targeting pre-defined product quality attributes, e.g., glycoform, to match the innovator's range. This review summarizes recent advances and discusses future possibilities in this area.

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Engineering of chaperone systems and of the unfolded protein response

Cited by 37 publications

References 171 publications

Improved antibody production in Chinese hamster ovary cells by ATF4 overexpression

Improved antibody production in Chinese hamster ovary cells by ATF4 overexpression

New strategy for rapid isolation of stable cell lines from DNA-transformed insect cells using fluorescence activated cell-sorting

Cell line development for biomanufacturing processes: recent advances and an outlook

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