Protein disulfide isomerase does not control recombinant IgG4 productivity in mammalian cell lines

Hayes, N.V.L. and Smales, C.M. and Klappa, P. (2009) Protein disulfide isomerase does not control recombinant IgG4 productivity in mammalian cell lines. Biotechnology and Bioengineering, 105 (4). pp. 770-779. ISSN 0006-3592. (The full text of this publication is not available from this repository)

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Official URL
http://dx.doi.org/10.1002/bit.22587

Abstract

Post-translational limitations in the endoplasmic reticulum during recombinant monoclonal antibody production are an important factor in lowering the capacity for synthesis and secretion of correctly folded proteins. Mammalian protein disulfide isomerase (PDI) has previously been shown to have a role in the formation of disulfide bonds in immunoglobulins. Several attempts have been made to improve the rate of recombinant protein production by overexpressing PDI but the results from these studies have been inconclusive. Here we examine the effect of (a) transiently silencing PDI mRNA and (b) increasing the intracellular levels of members of the PDI family (PDI, ERp72, and PDIp) on the mRNA levels, assembly and secretion of an IgG4 isotype. Although transiently silencing PDI in NS0/2N2 cells suggests that PDI is involved in disulfide bond formation of this subclass of antibody, our results show that PDI does not control the overall IgG4 productivity. Furthermore, overexpression of members of the PDI family in a Chinese hamster ovary (CHO) cell line does not improve productivity and hence we conclude that the catalysis of disulfide bond formation is not rate limiting for IgG4 production.

Item Type: Article
Uncontrolled keywords: control;disulfide bonds;mammalian cells;monoclonal antibody productivity;protein disulfide isomerase
Subjects: Q Science
Divisions: Faculties > Science Technology and Medical Studies > School of Biosciences
Depositing User: Sue Davies
Date Deposited: 28 Mar 2012 14:16
Last Modified: 03 Apr 2012 10:47
Resource URI: http://kar.kent.ac.uk/id/eprint/29226 (The current URI for this page, for reference purposes)
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