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Mammalian Cell Line Developments in Speed and Efficiency

Part of the Advances in Biochemical Engineering/Biotechnology book series (ABE,volume 139)

Keywords

  • Automation
  • Bioprocess development
  • Cell engineering
  • Chinese Hamster Ovary cells
  • Protein expression

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  • DOI: 10.1007/10_2013_260
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Fig. 1
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References

  1. Bailey KM (2008) Balancing the need for speed during development of early-stage clinical versus late-stage commercial antibody processes. Optimising Biomanufacturing Processes (oral presentation)

    Google Scholar 

  2. Bebbington C, Renner G, Thomson S et al (1992) High-level expression of a recombinant antibody from myeloma cells using a glutamine synthetase gene as an amplifiable selectable marker. Nat Biotech 10:169–175

    CAS  CrossRef  Google Scholar 

  3. Benton T, Chen T, McEntee M et al (2002) The use of UCOE vectors in combination with a preadapted serum free suspension cell line allows for rapid production of large quantities of protein. Cytotechnol 38:43–46

    CAS  CrossRef  Google Scholar 

  4. Bianchi A, McGrew J (2003) High-level expression of full-length antibodies using trans-complementing expression vectors. Biotechnol Bioeng 84(4):439–444

    CAS  CrossRef  Google Scholar 

  5. Bosques C, Collins B, Meador J et al (2010) Chinese Hamster Ovary cells can produce galactose-α-1,3-galactose antigens on proteins. Nat Biotechnol 28(11):1153–1156

    CAS  CrossRef  Google Scholar 

  6. Brezinsky S, Chiang G, Szilvasi A et al (2003) A simple method for enriching populations of transfected CHO cells for cells of higher specific productivity. J Immunol Methods 277:141–155

    CAS  CrossRef  Google Scholar 

  7. Burgess D (2013) Technology: a CRISPR genome-editing tool. Nat Rev Genet 14(2):80

    CAS  CrossRef  Google Scholar 

  8. Cabaniols J, Paques F (2008) Robust cell line development using meganucleases. Methods Mol Biol 435:31–45

    CAS  CrossRef  Google Scholar 

  9. Cairns V, DeMaria C, Poulin F et al (2011) Utilization of non-AUG initiation codons in a flow cytometric method for efficient selection of recombinant cell lines. Biotechnol Bioeng 108(11):2611–2622

    CAS  CrossRef  Google Scholar 

  10. Campbell M, Corisdeo S, McGee C, Kraichely D (2010) Utilization of site-specific recombination for generating therapeutic protein producing cell lines. Mol Biotechnol 45:199–202

    CAS  CrossRef  Google Scholar 

  11. Caron A, Nicolas C, Gaillet B et al (2009) Fluorescent labeling in semi-solid medium for selection of mammalian cells secreting high-levels of recombinant proteins. BMC Biotechnol 9:42

    CrossRef  Google Scholar 

  12. Christian M, Cermak T, Doyle E et al (2010) Targeting DNA double-strand breaks with TAL effector nucleases. Genetics 186(2):757–761

    CAS  CrossRef  Google Scholar 

  13. Chung C, Mirakhur B, Chan E et al (2008) Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med 358(11):1109–1117

    CAS  CrossRef  Google Scholar 

  14. Clarke C, Henry M, Doolan P, Kelly S, Aherne S, Sanchez N, Kelly P, Kinsella P, Breen L, Madden SF, Zhang L, Leonard M, Clynes M, Meleady P, Barron N (2012) Integrated miRNA, mRNA and protein expression analysis reveals the role of post-transcriptional regulation in controlling CHO cell growth rate. BMC Genomics 13:656

    CAS  CrossRef  Google Scholar 

  15. Cockett M, Bebbington C, Yarranton G (1991) The use of engineered E1A genes to transactivate the hCMV-MIE promoter in permanent CHO cell lines. Nucleic Acids Res 19(2):319–325

    CAS  CrossRef  Google Scholar 

  16. Coffman JL, Kramarczyk JF, Kelley BD (2008) High-throughput screening of chromatographic separations: I. Method development and column modeling. Biotech Bioeng 100(4):605–618

    Google Scholar 

  17. Combs RG, Yu E, Roe S et al (2011) Fed-batch bioreactor performance and cell line stability evaluation of the artificial chromosome expression technology expressing an IgG1 in Chinese hamster ovary cells. Biotechnol Prog 27(1):201–208

    CAS  CrossRef  Google Scholar 

  18. Doolan P, Melville M, Gammell P, Sinacore M, Meleady P, McCarthy K, Francullo L, Leonard M, Charlebois T, Clynes M (2008) Transcriptional profiling of gene expression changes in a PACE-transfected CHO DUKX cell line secreting high levels of rhBMP-2. Mol Biotechnol 39(3):187–199

    CAS  CrossRef  Google Scholar 

  19. DeMaria C, Cairns V, Schwarz C et al (2007) Accelerated clone selection for recombinant CHO cells using a FACS based high throughput screen. Biotechnol Prog 23(2):465–472

    CAS  CrossRef  Google Scholar 

  20. Deetz JS (2008) Realizing the vision of biology over steel: Wyeth BioPharma’s strategy for platform process development. The 236th ACS National Meeting (Oral presentation)

    Google Scholar 

  21. Essers R, Kewes H, Schiedner G (2011) Improving volumetric productivity of a stable human CAP cell line by bioprocess optimization. BMC Proc 5(Suppl 8):66

    CrossRef  Google Scholar 

  22. Fan L, Kadura I, Krebs L et al (2012) Improving the efficiency of CHO cell line generation using glutamine synthetase gene knockout cells. Biotechnol Bioeng 109(4):1007–1015

    CAS  CrossRef  Google Scholar 

  23. Ferrara C, Brunker P, Suter T et al (2006) Modulation of therapeutic antibody effector functions by glycosylation engineering: influence of Golgi enzyme localization domain and co-expression of heterologous beta1, 4-N-acetylglucosaminyltransferase III and Golgi alpha-mannosidase II. Biotechnol Bioeng 93(5):851–861

    CAS  CrossRef  Google Scholar 

  24. Figueroa B, Ailor E, Osborne D et al (2007) Enhanced cell culture performance using inducible anti-apoptotic genes E1B-19K and Aven in the production of a monoclonal antibody with Chinese hamster ovary cells. Biotechnol Bioeng 97(4):877–892

    CAS  CrossRef  Google Scholar 

  25. Gammell P, Barron N, Kumar N, Clynes M (2007) Initial identification of low temperature and culture stage induction of miRNA expression in suspension CHO-K1 cells. J Biotechnol 130(3):213–218

    CAS  CrossRef  Google Scholar 

  26. Ghaderi D, Taylor R, Padler-Karavani V et al (2010) Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic glycoproteins. Nat Biotechnol 28(8):863–867

    CAS  CrossRef  Google Scholar 

  27. Girod PA, Nguyen DQ, Calabrese D, Puttini S, Grandjean M, Martinet D, Regamey A, Saugy D, Beckmann JS, Bucher P, Mermod N (2007) Genome-wide prediction of matrix attachment regions that increase gene expression in mammalian cells. Nat Methods 4(9):747–753

    CAS  CrossRef  Google Scholar 

  28. Grandjean M, Girod P-A, Calabrese D, Kostyrko K, Wicht W, Yerly F, Mazza C, Beckmann JS, Martinet D, Mermod N (2011) High-level transgene expression by homologous recombination-mediated gene transfer. Nuc Acids Res 39(15):e104

    CAS  CrossRef  Google Scholar 

  29. Haines A (2012) Use of islands of automation for cell line development. IBC Cell Line Dev & Eng

    Google Scholar 

  30. Hammond S, Kaplarevic M, Borth N, Betenbaugh MJ, Lee KH (2012) Chinese hamster genome database: an online resource for the CHO community at www.CHOgenome.org. Biotechnol Bioeng 109(6):1353–1356

  31. Houston JG, Banks MN, Binnie A, Brenner S, O’Connell J, Petrillo EW (2008) Case study: impact of technology investment on lead discovery at Bristol-Myers Squibb, 1998–2006. Drug Disc Today 13(1/2):44–51

    CrossRef  Google Scholar 

  32. Huang Y, Li Y, Wang YG, Gu X, Wang Y, Shen BF (2007) An efficient and targeted gene integration system for high-level antibody expression. J Immunol Methods 322:28–39

    CAS  CrossRef  Google Scholar 

  33. Huggett B, Lahteenmaki R (2012) Public biotech 2011-the numbers. Nat Biotechnol 30(8):751–757

    CAS  CrossRef  Google Scholar 

  34. Jadhav V, Hackly M, Bort J et al (2012) screening method to assess biological effects of microRNA overexpression in Chinese hamster ovary cells. Biotechnol Bioeng 109(6):1376–1385

    CAS  CrossRef  Google Scholar 

  35. Jones D, Kroos N, Anema R et al (2003) High-level expression of recombinant IgG in the human cell line per.c6. Biotechnol Prog 19(1):163–168

    CAS  CrossRef  Google Scholar 

  36. Kanda Y, Imai-Nishiya H, Kuni-Kamochi R et al (2007) Establishment of a GDP-mannose 4,6-dehydratase (GMD) knockout host cell line: a new strategy for generating completely non-fucosylated recombinant therapeutics. J Biotechnol 130(3):300–310

    CAS  CrossRef  Google Scholar 

  37. Kanda Y, Yamane-Ohnuki N, Sakai N et al (2006) Comparison of cell lines for stable production of fucose-negative antibodies with enhanced ADCC. Biotechnol Bioeng 94(4):680–688

    CAS  CrossRef  Google Scholar 

  38. Kennard ML, Goosney DL, Monteith D, Zhang L, Moffat M, Fischer D, Mott J (2009) The generation of stable, high MAb expressing CHO cell lines based on the Artificial Chromosome Expression (ACE) technology. Biotech Bioeng 104(3):540–553

    CAS  CrossRef  Google Scholar 

  39. Kim JY, Kim Y-G, Lee GM (2012) CHO cells in biotechnology for production of recombinant proteins: current state and further potential. Appl Microbiol Biotechnol 93:917–930

    CAS  CrossRef  Google Scholar 

  40. Kito M, Itami S, Fukano Y, Yamana K, Shibui T (2002) Construction of engineered CHO strains for high-level production of recombinant proteins. Appl Microbiol Biotechnol 60:442–448

    CAS  CrossRef  Google Scholar 

  41. Kober L, Zehe C, Bode J (2012) Development of a novel ER stress based selection system for the isolation of highly productive clones. Biotechnol Bioeng 109(10):2599–2611

    CAS  CrossRef  Google Scholar 

  42. Kramer O, Klausing S, Noll T (2010) Methods in mammalian cell line engineering: from random mutagenesis to sequence-specific approaches. Appl Microbiol Biotechnol 88:425–436

    CrossRef  Google Scholar 

  43. Kwaks T, Barnett P, Hemrika W et al (2003) Identification of anti-repressor elements that confer high and stable protein production in mammalian cells. Nat Biotechnol 21(5):553–558

    CAS  CrossRef  Google Scholar 

  44. Lee E, Roth J, Paulson J (1989) Alteration of terminal glycosylation sequences on N-linked oligosaccharides of Chinese hamster ovary cells by expression of beta-galactoside alpha 2,6-sialyltransferase. J Biol Chem 264(23):13848–13855

    CAS  Google Scholar 

  45. Lee K, Jin X, Zhang K et al (2003) A biochemical and pharmacological comparison of enzyme replacement therapies for the glycolipid storage disorder Fabry disease. Glycobio 13(4):305–313

    CrossRef  Google Scholar 

  46. Lee Y, Wong K, Tan J et al (2009) Overexpression of heat shock proteins (HSPs) in CHO cells for extended culture viability and improved recombinant protein production. J Biotechnol 143:34–43

    CAS  CrossRef  Google Scholar 

  47. Legman R, Schreyer HB, Combs RG, McCormick EL, Russo AP, Rodgers ST (2009) A predictive high-throughput scale-down model of monoclonal antibody production in CHO cells. Biotech Bioeng 104(6):1107–1120

    CrossRef  Google Scholar 

  48. Lindenbaum M, Perkins E, Csonka E et al (2004) A mammalian artificial chromosome engineering system (ACE System) applicable to biopharmaceutical protein production, transgenesis, and gene-based cell therapy. Nuc Acids Res 32(21):e172

    CrossRef  Google Scholar 

  49. Liu P, Chan E, Cost G et al (2010) Generation of a triple-gene knockout mammalian cell line using engineered zinc-finger nucleases. Biotechnol Bioeng 106(1):97–105

    CAS  Google Scholar 

  50. Llop E, Gutierrez-Gallego R, Segura J et al (2008) Structural analysis of the glycosylation of gene-activated erythropoietin (epoetin delta, Dynepo). Anal Biocehm 383:243–254

    CAS  CrossRef  Google Scholar 

  51. Meng Y, Liang J, Wong W et al (2000) Green fluorescent protein as a second selectable marker for selection of high producing clones from transfected CHO cells. Gene 242:201–207

    Google Scholar 

  52. Mohan C, Kim Y, Koo J, Lee G (2008) Assessment of cell engineering strategies for improved therapeutic protein production in CHO cells. Biotechnol J 3(5):624–630

    CAS  CrossRef  Google Scholar 

  53. Nagy A (2000) Cre recombinase: the universal reagent for genome tailoring. Genesis 26:99–109

    CAS  CrossRef  Google Scholar 

  54. Nehlsen K, Schucht R, de Gamma-Norton L, Krömer W, Baer A, Cayli A, Hauser H, Wirth D (2009) Recombinant protein expression by targeting pre-selected chromosomal loci. BMC Biotechnol 9:100

    CrossRef  Google Scholar 

  55. Nieminen M, Tuuri T, Savilahti H (2010) Genetic recombination pathways and their application for genome modification of human embryonic stem cells. Exp Cell Res 316(16):2578–2586

    CAS  CrossRef  Google Scholar 

  56. Noguchi A, Mukuria C, Suzuki E et al (1995) Immunogenicity of N-glycolylneuraminic acid-containing carbohydrate chains of recombinant human erythropoietin expressed in Chinese Hamster Ovary Cells. J Biochem 117(1):59–62

    CAS  Google Scholar 

  57. Paulin RP, Ho T, Balzer HJ, Holliday R (1998) Gene silencing by DNA methylation and dual inheritance in Chinese Hamster Ovary Cells. Genetics 149:1081–1088

    CAS  Google Scholar 

  58. Prajapati S (2012) High-throughput analytical platforms for cell line and process development. IBC 9th bioprocess international conference and exhibition

    Google Scholar 

  59. Prentice H, Ehrenfels B, Sisk W (2007) Improving performance of mammalian cells in fed-batch processes through “bioreactor evolution”. Biotechnol Prog 23:458–464

    CAS  CrossRef  Google Scholar 

  60. Russell J (2012) Improving cell culture optimization. Gen Eng Biotechnol News 32(7)

    Google Scholar 

  61. Schlake T, Bode J (1994) Use of mutated FLP recognition target (FRT) sites for the exchange of expression cassettes at defined chromosomal loci. Biochem 33(43):12746–12751

    CAS  CrossRef  Google Scholar 

  62. Shahrokh Z, Royle L, Saldova R et al (2011) Erythropoietin produced in a human cell line (Dynepo) has significant differences in glycosylation compared with erythropoietins produced in CHO cell lines. Mol Pharm 8(1):286–296

    CAS  CrossRef  Google Scholar 

  63. Shields R, Lai J, Keck R et al (2002) Lack of fucose on human IgG1N-linked oligosaccharide improves binding to human Fcgamma RIII and antibody-dependent cellular toxicity. J Biol Chem 277(300):26733–26740

    CAS  CrossRef  Google Scholar 

  64. Sinacore MS, Drapeau D, Adamson SR (1999) Adaptation of mammalian cells to growth in serum-free media. Animal Cell Biotech: Methods Biotech 8:11–22

    CAS  CrossRef  Google Scholar 

  65. Sleiman R, Gray P, McCall M et al (2008) Accelerated cell line development using two-color fluorescence activated cell sorting to select highly expressing antibody-producing clones. Biotechnol Bioeng 99(3):578–587

    CAS  CrossRef  Google Scholar 

  66. Tabuchi H, Sugiyama T (2013) Cooverexpression of alanine aminotransferase 1 in Chinese hamster ovary cells overexpressing taurine transporter further stimulates metabolism and enhances product yield. Biotechnol Bioeng

    Google Scholar 

  67. Tan H, Lee M, Yap M, Wang D (2008) Overexpression of cold-inducible RNA-binding protein increases interferon-gamma production in Chinese-hamster ovary cells. Biotechnol Appl Biocem 49:247–257

    CAS  CrossRef  Google Scholar 

  68. Tummala S, Titus M, Wilson L et al (2012) Evaluation of exogenous siRNA addition as a metabolic engineering tool for modifying biopharmaceuticals. Biotechnol Prog

    Google Scholar 

  69. Urlaub G, Chasin L (1980) Isolation of Chinese hamster cell mutants deficient in dihydrofolate reductase activity. Proc Natl Acad Sci 77:4216–4220

    CAS  CrossRef  Google Scholar 

  70. van Blockland H, Kwaks T, Sewalt R et al (2007) A novel high stringency selection system allows screening of few clones for high protein expression. J Biotechnol 128(2):237–245

    CrossRef  Google Scholar 

  71. von Horsten H, Ogorek C, Blanchard V et al (2010) Production of non-fucosylated antibodies by co-expression of heterologous GDP-6-deoxy-D-lyxo-4-hexulose reductase. Glycobiol 20(12):1607–1618

    CrossRef  Google Scholar 

  72. Wang Z, Gerstein M, Snyder M (2009) RNA-Seq: a revolutionary tool for transcriptomics. Nat Rev Genet 10(1):57–63

    CAS  CrossRef  Google Scholar 

  73. Westwood A, Rowe D, Clarke H (2010) Improved recombinant protein yield using a codon deoptimized DHFR selectable marker in a CHEF1 expression plasmid. Biotechnol Prog 26(6):1558–1566

    CAS  CrossRef  Google Scholar 

  74. Wong D, Wong K, Nissom P et al (2006) Targeting early apoptotic genes in batch and fed-batch CHO cell cultures. Biotechnol Bioeng 95(3):350–361

    CAS  CrossRef  Google Scholar 

  75. Xu X, Nagarajan H, Lewis N et al (2011) The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line. Nat Biotechnol 29:735–741

    CAS  CrossRef  Google Scholar 

  76. Yamane-Ohnuki N, Kinoshita S, Inoue-Urakubo M et al (2004) Establishment of FUT8 knockout Chinese Hamster Ovary cells: an ideal host cell line for producing completely defucosylated antibodies with enhanced antibody-dependent cellular cytotoxicity. Biotechnol Bioeng 87(5):614–622

    CAS  CrossRef  Google Scholar 

  77. Yee JC, de Leon GM, Philp RJ, Yap M, Hu WS (2008) Genomic and proteomic exploration of CHO and hybridoma cells under sodium butyrate treatment. Biotech Bioeng 99(5):1186–1204

    CAS  CrossRef  Google Scholar 

  78. Zahn-Zabal M, Kobr M, Girod P et al (2001) Development of stable cell lines for production or regulated expression using matrix attachment regions. J Biotechnol 87(1):29–42

    CAS  CrossRef  Google Scholar 

  79. Zhang M, Koskie K, Ross J et al (2010) Enhancing glycoprotein sialylation by targeted gene silencing in mammalian cells. Biotechnol Bioeng 105(6):1094–1105

    CAS  Google Scholar 

  80. Zhang P, Haryadi R, Chan K et al (2012) Identification of functional elements of the GDP-fucose transporter SLC35C1 using a novel Chinese hamster ovary mutant. Glycobiology 22(7):897–911

    CAS  CrossRef  Google Scholar 

  81. Zhou M, Crawford Y, Ng D et al (2011) Decreasing lactate level and increasing antibody production in Chinese Hamster Ovary cells (CHO) by reducing the expression of lactate dehydrogenase and pyruvate dehydrogenase kinases. J Biotechnol 153:27–34

    CAS  CrossRef  Google Scholar 

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Estes, S., Melville, M. (2013). Mammalian Cell Line Developments in Speed and Efficiency. In: Zhou, W., Kantardjieff, A. (eds) Mammalian Cell Cultures for Biologics Manufacturing. Advances in Biochemical Engineering/Biotechnology, vol 139. Springer, Berlin, Heidelberg. https://doi.org/10.1007/10_2013_260

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