Improving the secretory capacity of Chinese hamster ovary cells by ectopic expression of effector genes: Lessons learned and future directions

被引:58
作者
Hansen, Henning Gram [1 ]
Pristovsek, Nusa [1 ]
Kildegaard, Helene Faustrup [1 ]
Lee, Gyun Min [1 ,2 ]
机构
[1] Tech Univ Denmark, Novo Nordisk Fdn Ctr Biosustainabil, Lyngby, Denmark
[2] Korea Adv Inst Sci & Technol, Dept Biol Sci, 291 Daehak Ro, Daejeon 305701, South Korea
关键词
Cell engineering; Chinese hamster ovary (CHO) cells; Ectopic expression; Endoplasmic reticulum; ER stress; Gene dosage; Product quality; Recombinant protein production; Secretion bottleneck; Specific productivity; RECOMBINANT PROTEIN-PRODUCTION; MONOCLONAL-ANTIBODY PRODUCTION; CHO-CELLS; ENDOPLASMIC-RETICULUM; DISULFIDE-ISOMERASE; MAMMALIAN-CELLS; MESSENGER-RNA; THROMBOPOIETIN PRODUCTIVITY; TRANSIENT TRANSFECTION; TRANSLATION INITIATION;
D O I
10.1016/j.biotechadv.2016.11.008
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Chinese hamster ovary (CHO) cells are the preferred cell factory for the production of therapeutic glycoproteins. Although efforts primarily within bioprocess optimization have led to increased product titers of recombinant proteins (r-proteins) expressed in CHO cells, post-transcriptional bottlenecks in the biosynthetic pathway of r-proteins remain to be solved. To this end, the ectopic expression of transgenes (effector genes) offers great engineering potential. However, studies on effector genes have in some cases led to inconsistent results. Whereas this can in part be attributed to product specificity, other experimental and cellular factors are likely important contributors to these conflicting results. Here, these factors are reviewed and discussed with the objective of guiding future studies on effector genes. (C) 2016 Elsevier Inc. All rights reserved.
引用
收藏
页码:64 / 76
页数:13
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