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mRNA stability and antibody production in CHO cells: Improvement through gene optimization
Author(s) -
Hung Finn,
Deng Liang,
Ravnikar Paula,
Condon Russ,
Li Benson,
Do Lien,
Saha Deba,
Tsao YungShyeng,
Merchant Ankit,
Liu Zhong,
Shi Shuangping
Publication year - 2010
Publication title -
biotechnology journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.144
H-Index - 84
eISSN - 1860-7314
pISSN - 1860-6768
DOI - 10.1002/biot.200900192
Subject(s) - chinese hamster ovary cell , antibody , recombinant dna , transfection , gene , cell culture , gene expression , immunoglobulin light chain , microbiology and biotechnology , biology , messenger rna , coding region , chemistry , biochemistry , immunology , genetics
Abstract The productivity of stably transfected cell lines is of critical importance for the manufacturing of therapeutic proteins. Various methods have been successfully implemented to increase the production output of mammalian cell cultures. Increasing evidence suggests that optimization of the gene coding sequences of an expression vector can improve specific cell line yield of the recombinant protein. Here we demonstrate that gene optimization substantially enhances antibody production in Chinese hamster ovary cells. When gene optimization was applied to the heavy and light chain genes of a therapeutic antibody, we observed increased antibody production in transient transfection. Elevated heavy chain mRNA level was associated with the increase of antibody production. Further analysis suggested that the increased antibody expression is attributable to enhanced mRNA stability resulting from gene optimization. Gene optimization also led to increased antibody production in stable clones.