The art of CHO cell engineering: A comprehensive retrospect and future perspectives

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• 作者：Simon Fischer^a ; ^b ; ^{simon.fischer@boehringer-ingelheim.com" class="auth_mail" title="E-mail the corresponding author} ; René ; Handrick^a ; Kerstin Otte^a
• 关键词：AAV ; adeno-associated virus ; ADCC ; antibody-dependent cellular cytotoxicity ; cDNA ; complementary DNA ; cgr ; Cricetulus griseus ; CHO ; Chinese hamster ovary ; CRISPR ; clustered regularly interspaced short palindromic repeats ; DHFR ; dihydrofolate reductase ; miRNA ; microRNA ; GFP ; green-fluorescent protein ; GOI ; gene of interest ; GS ; glutamine synthetase ; hsa ; Homo sapiens ; pDNA ; plasmid DNA ; PTM ; post-translational modifications ; RISC ; RNA-induced silencing complex ; RNAi ; RNA interference ; shRNA ; smal
• 刊名：Biotechnology Advances
• 出版年：2015
• 出版时间：December 2015
• 年：2015
• 卷：33
• 期：8
• 页码：1878-1896
• 全文大小：1246 K

文摘

Chinese hamster ovary (CHO) cells represent the most frequently applied host cell system for industrial manufacturing of recombinant protein therapeutics. CHO cells are capable of producing high quality biologics exhibiting human-like post-translational modifications in gram quantities. However, production processes for biopharmaceuticals using mammalian cells still suffer from cellular limitations such as limited growth, low productivity and stress resistance as well as higher expenses compared to bacterial or yeast based expression systems. Besides bioprocess, media and vector optimizations, advances in host cell engineering technologies comprising introduction, knock-out or post-transcriptional silencing of engineering genes have paved the way for remarkable achievements in CHO cell line development. Furthermore, thorough analysis of cellular pathways and mechanisms important for bioprocessing steadily unravels novel target molecules which might be addressed by functional genomic tools in order to establish superior production cell factories. This review provides a comprehensive summary of the most fundamental achievements in CHO cell engineering over the past three decades. Finally, the authors discuss the potential of novel and innovative methodologies that might contribute to further enhancement of existing CHO based production platforms for biopharmaceutical manufacturing in the future.