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

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• 作者：Henning Gram Hansen^a ; ^{hgra@biosustain.dtu.dk} ; Nu&scaron ; a Pristov&scaron ; ek^a ; Helene Faustrup Kildegaard^a ; Gyun Min Lee^a ; ^b ; ^{gyunminlee@kaist.ac.kr}
• 关键词：ATF6c ; activating transcription factor 6 ; CHO ; Chinese hamster ovary ; DHFR ; dihydrofolate reductase ; effector gene ; a transgene ectopically expressed with the purpose of obtaining a phenotypic change ; IE ; inducible expression ; EPO ; erythropoietin ; ER ; endoplasmic reticulum ; HEK ; human embryonic kidney ; MAb ; monoclonal antibody ; pcd ; pg per cell per day ; PDI ; protein disulphide isomerase ; PTM ; post-translational modification ; qp ; specific protein productivity ; r-protein ; recombinant protein ; SCS
• 刊名：Biotechnology Advances
• 出版年：2017
• 出版时间：January-February 2017
• 年：2017
• 卷：35
• 期：1
• 页码：64-76
• 全文大小：757 K
• 卷排序：35

文摘

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.