Skip to main content
SpringerLink
Log in

CHO Glycosylation Mutants as Potential Host Cells to Produce Therapeutic Proteins with Enhanced Efficacy

  • Chapter
  • First Online:
Future Trends in Biotechnology

Part of the book series: Advances in Biochemical Engineering/Biotechnology ((ABE,volume 131))

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

Abbreviations

AAL:

Aleuria aurantia lectin

ADCC:

Antibody-dependent cellular cytotoxicity

CDC:

Complement-dependent cytotoxicity

CDG:

Congenital disorder of glycosylation

CHO:

Chinese hamster ovary

Con A:

Concanavalin A

CST:

CMP-sialic acid transporter

EPO:

Erythropoietin

ER:

Endoplasmic reticulum

ERT:

Enzyme replacement therapy

Gal:

Galactose

GalNAc:

N-acetylgalactosamine

GCase:

Glucocerebrosidase

G-CSF:

Granulocyte-colony stimulating factor

GlcNAc:

N-acetylglucosamine

GnT I:

N-acetylglucosaminyltransferase I

HPAEC-PAD:

High pH anion exchange chromatography with pulsed amperometric detection

IgG:

Immunoglobulin G

IFN:

Interferon

MAA:

Maackia amurensis agglutinin

MALDI-TOF:

Matrix-assisted laser desorption/ionization coupled with a time-of-flight analyzer

Man:

Mannose

MS:

Mass spectrometry

Neu5Gc:

N-glycolylneuraminic acid

NST:

Nucleotide sugar transporter

RCA:

Ricinus communis agglutinin

Sia:

Sialic acid

UGnT:

UDP-GlcNAc transporter

UGT:

UDP-galactose transporter

ZFN:

Zinc-finger nuclease

References

  1. Walsh G (2000) Biopharmaceutical benchmarks. Nat Biotechnol 18(8):831–833

    Article  CAS  Google Scholar 

  2. Walsh G (2003) Biopharmaceutical benchmarks–2003. Nat Biotechnol 21(8):865–870

    Article  CAS  Google Scholar 

  3. Walsh G, Jefferis R (2006) Post-translational modifications in the context of therapeutic proteins. Nat Biotechnol 24(10):1241–1252

    Article  CAS  Google Scholar 

  4. Walsh G (2010) Biopharmaceutical benchmarks 2010. Nat Biotechnol 28(9):917–924

    Article  CAS  Google Scholar 

  5. Ghaderi D, Taylor RE, Padler-Karavani V, Diaz S, Varki A (2010) Implications of the presence of N-glycolylneuraminic acid in recombinant therapeutic glycoproteins. Nat Biotechnol 28(8):863–867

    Article  CAS  Google Scholar 

  6. Elliott S, Lorenzini T, Asher S, Aoki K, Brankow D, Buck L, Busse L, Chang D, Fuller J, Grant J, Hernday N, Hokum M, Hu S, Knudten A, Levin N, Komorowski R, Martin F, Navarro R, Osslund T, Rogers G, Rogers N, Trail G, Egrie J (2003) Enhancement of therapeutic protein in vivo activities through glycoengineering. Nat Biotechnol 21(4):414–421

    Article  CAS  Google Scholar 

  7. Hossler P, Khattak SF, Li ZJ (2009) Optimal and consistent protein glycosylation in mammalian cell culture. Glycobiology 19(9):936–949

    Article  CAS  Google Scholar 

  8. Parodi AJ (2000) Protein glucosylation and its role in protein folding. Annu Rev Biochem 69:69–93

    Article  CAS  Google Scholar 

  9. Haltiwanger RS, Lowe JB (2004) Role of glycosylation in development. Annu Rev Biochem 73:491–537

    Article  CAS  Google Scholar 

  10. International Conference on Harmonisation; guidance on specifications: test procedures and acceptance criteria for biotechnological/biological products. Notice. Food and Drug Administration, HHS (1999). Fed Regist 64 (159):44928–44935

    Google Scholar 

  11. International Conference on Harmonisation; guidance on Q5E Comparability of Biotechnological/Biological Products Subject to Changes in Their Manufacturing Process; availability. Notice (2005). Fed Regist 70 (125):37861–37862

    Google Scholar 

  12. Patnaik SK, Stanley P (2006) Lectin-resistant CHO glycosylation mutants. Methods Enzymol 416:159–182

    Article  CAS  Google Scholar 

  13. North SJ, Huang HH, Sundaram S, Jang-Lee J, Etienne AT, Trollope A, Chalabi S, Dell A, Stanley P, Haslam SM (2010) Glycomics profiling of Chinese hamster ovary cell glycosylation mutants reveals N-glycans of a novel size and complexity. J Biol Chem 285(8):5759–5775

    Article  CAS  Google Scholar 

  14. Hoppe H (2000) Cerezyme–recombinant protein treatment for Gaucher’s disease. J Biotechnol 76(2–3):259–261

    Article  CAS  Google Scholar 

  15. Shinkawa T, Nakamura K, Yamane N, Shoji-Hosaka E, Kanda Y, Sakurada M, Uchida K, Anazawa H, Satoh M, Yamasaki M, Hanai N, Shitara K (2003) The absence of fucose but not the presence of galactose or bisecting N-acetylglucosamine of human IgG1 complex-type oligosaccharides shows the critical role of enhancing antibody-dependent cellular cytotoxicity. J Biol Chem 278(5):3466–3473

    Article  CAS  Google Scholar 

  16. Le Provost F, Lillico S, Passet B, Young R, Whitelaw B, Vilotte JL (2010) Zinc finger nuclease technology heralds a new era in mammalian transgenesis. Trends Biotechnol 28(3):134–141

    Article  Google Scholar 

  17. Lim SF, Lee MM, Zhang P, Song Z (2008) The Golgi CMP-sialic acid transporter: a new CHO mutant provides functional insights. Glycobiology 18(11):851–860

    Article  CAS  Google Scholar 

  18. Chan KF, Zhang P, Song Z (2010) Identification of essential amino acid residues in the hydrophilic loop regions of the CMP-sialic acid transporter and UDP-galactose transporter. Glycobiology 20(6):689–701

    Article  CAS  Google Scholar 

  19. Zhang P, Haryadi R, Chan KF, Teo G, Goh J, Pereira NA, Feng H, Song Z (2012) Identification of functional elements of the GDP-fucose transporter SLC35C1 using a novel Chinese hamster ovary mutant. Glycobiology 22(7):897–911

    Article  CAS  Google Scholar 

  20. Siminovitch L (1976) On the nature of hereditable variation in cultured somatic cells. Cell 7(1):1–11

    Article  CAS  Google Scholar 

  21. Martinez-Duncker I, Dupre T, Piller V, Piller F, Candelier JJ, Trichet C, Tchernia G, Oriol R, Mollicone R (2005) Genetic complementation reveals a novel human congenital disorder of glycosylation of type II, due to inactivation of the Golgi CMP-sialic acid transporter. Blood 105(7):2671–2676

    Article  CAS  Google Scholar 

  22. Wang WC, Cummings RD (1988) The immobilized leukoagglutinin from the seeds of Maackia amurensis binds with high affinity to complex-type Asn-linked oligosaccharides containing terminal sialic acid-linked alpha-2,3 to penultimate galactose residues. J Biol Chem 263(10):4576–4585

    CAS  Google Scholar 

  23. Knibbs RN, Goldstein IJ, Ratcliffe RM, Shibuya N (1991) Characterization of the carbohydrate binding specificity of the leukoagglutinating lectin from Maackia amurensis. Comparison with other sialic acid-specific lectins. J Biol Chem 266(1):83–88

    CAS  Google Scholar 

  24. Sharon N, Lis H (2004) History of lectins: from hemagglutinins to biological recognition molecules. Glycobiology 14(11):53R–62R

    Article  CAS  Google Scholar 

  25. Li WW, Yu JY, Xu HL, Bao JK (2011) Concanavalin A: a potential anti-neoplastic agent targeting apoptosis, autophagy and anti-angiogenesis for cancer therapeutics. Biochem Biophys Res Commun 414(2):282–286

    Article  CAS  Google Scholar 

  26. Lim SF, Chuan KH, Liu S, Loh SO, Chung BY, Ong CC, Song Z (2006) RNAi suppression of Bax and Bak enhances viability in fed-batch cultures of CHO cells. Metab Eng 8(6):509–522

    Article  CAS  Google Scholar 

  27. Goh JS, Zhang P, Chan KF, Lee MM, Lim SF, Song Z (2010) RCA-I-resistant CHO mutant cells have dysfunctional GnT I and expression of normal GnT I in these mutants enhances sialylation of recombinant erythropoietin. Metab Eng 12(4):360–368

    Article  CAS  Google Scholar 

  28. Harduin-Lepers A, Vallejo-Ruiz V, Krzewinski-Recchi MA, Samyn-Petit B, Julien S, Delannoy P (2001) The human sialyltransferase family. Biochimie 83(8):727–737

    Article  CAS  Google Scholar 

  29. Baenziger JU, Fiete D (1979) Structural determinants of Ricinus communis agglutinin and toxin specificity for oligosaccharides. J Biol Chem 254(19):9795–9799

    CAS  Google Scholar 

  30. Iskratsch T, Braun A, Paschinger K, Wilson IB (2009) Specificity analysis of lectins and antibodies using remodeled glycoproteins. Anal Biochem 386(2):133–146

    Article  CAS  Google Scholar 

  31. Chen W, Stanley P (2003) Five Lec1 CHO cell mutants have distinct Mgat1 gene mutations that encode truncated N-acetylglucosaminyltransferase I. Glycobiology 13(1):43–50

    Article  CAS  Google Scholar 

  32. Carroll D, Morton JJ, Beumer KJ, Segal DJ (2006) Design, construction and in vitro testing of zinc finger nucleases. Nat Protoc 1(3):1329–1341

    Article  CAS  Google Scholar 

  33. Maeder ML, Thibodeau-Beganny S, Osiak A, Wright DA, Anthony RM, Eichtinger M, Jiang T, Foley JE, Winfrey RJ, Townsend JA, Unger-Wallace E, Sander JD, Muller-Lerch F, Fu F, Pearlberg J, Gobel C, Dassie JP, Pruett-Miller SM, Porteus MH, Sgroi DC, Iafrate AJ, Dobbs D, McCray PB Jr, Cathomen T, Voytas DF, Joung JK (2008) Rapid “open-source” engineering of customized zinc-finger nucleases for highly efficient gene modification. Mol Cell 31(2):294–301

    Article  CAS  Google Scholar 

  34. Urnov FD, Miller JC, Lee YL, Beausejour CM, Rock JM, Augustus S, Jamieson AC, Porteus MH, Gregory PD, Holmes MC (2005) Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature 435(7042):646–651

    Article  CAS  Google Scholar 

  35. Doyon Y, McCammon JM, Miller JC, Faraji F, Ngo C, Katibah GE, Amora R, Hocking TD, Zhang L, Rebar EJ, Gregory PD, Urnov FD, Amacher SL (2008) Heritable targeted gene disruption in zebrafish using designed zinc-finger nucleases. Nat Biotechnol 26(6):702–708

    Article  CAS  Google Scholar 

  36. Santiago Y, Chan E, Liu PQ, Orlando S, Zhang L, Urnov FD, Holmes MC, Guschin D, Waite A, Miller JC, Rebar EJ, Gregory PD, Klug A, Collingwood TN (2008) Targeted gene knockout in mammalian cells by using engineered zinc-finger nucleases. Proc Natl Acad Sci USA 105(15):5809–5814

    Article  CAS  Google Scholar 

  37. Kim HJ, Lee HJ, Kim H, Cho SW, Kim JS (2009) Targeted genome editing in human cells with zinc finger nucleases constructed via modular assembly. Genome Res 19(7):1279–1288

    Article  CAS  Google Scholar 

  38. Dreier B, Segal DJ, Barbas CF 3rd (2000) Insights into the molecular recognition of the 5’-GNN-3’ family of DNA sequences by zinc finger domains. J Mol Biol 303(4):489–502

    Article  CAS  Google Scholar 

  39. Liu Q, Xia Z, Zhong X, Case CC (2002) Validated zinc finger protein designs for all 16 GNN DNA triplet targets. J Biol Chem 277(6):3850–3856

    Article  CAS  Google Scholar 

  40. Segal DJ, Dreier B, Beerli RR, Barbas CF 3rd (1999) Toward controlling gene expression at will: selection and design of zinc finger domains recognizing each of the 5’-GNN-3’ DNA target sequences. Proc Natl Acad Sci USA 96(6):2758–2763

    Article  CAS  Google Scholar 

  41. Sander JD, Zaback P, Joung JK, Voytas DF, Dobbs D (2007) Zinc finger targeter (ZiFiT): an engineered zinc finger/target site design tool. Nucleic Acids Res 35 (Web Server issue):W599–605

    Google Scholar 

  42. Sander JD, Maeder ML, Reyon D, Voytas DF, Joung JK, Dobbs D (2010) ZiFiT (Zinc Finger Targeter): an updated zinc finger engineering tool. Nucleic Acids Res 38 (Web Server issue):W462–468

    Google Scholar 

  43. Miller JC, Holmes MC, Wang J, Guschin DY, Lee YL, Rupniewski I, Beausejour CM, Waite AJ, Wang NS, Kim KA, Gregory PD, Pabo CO, Rebar EJ (2007) An improved zinc-finger nuclease architecture for highly specific genome editing. Nat Biotechnol 25(7):778–785

    Article  CAS  Google Scholar 

  44. Haryadi R, Zhang P, Chan KF, Song Z (2012) CHO-gmt5, a novel CHO glycosylation mutant for producing afucosylated and asialylated recombinant antibodies. Bioengineered 4(2):1–5

    Google Scholar 

  45. Zhang P, Tan DL, Heng D, Wang T, Mariati Yang Y, Song Z (2010) A functional analysis of N-glycosylation-related genes on sialylation of recombinant erythropoietin in six commonly used mammalian cell lines. Metab Eng 12(6):526–536

    Article  CAS  Google Scholar 

  46. North SJ, Hitchen PG, Haslam SM, Dell A (2009) Mass spectrometry in the analysis of N-linked and O-linked glycans. Curr Opin Struct Biol 19(5):498–506

    Article  CAS  Google Scholar 

  47. Markely LR, Ong BT, Hoi KM, Teo G, Lu MY, Wang DI (2010) A high-throughput method for quantification of glycoprotein sialylation. Anal Biochem 407(1):128–133

    Article  CAS  Google Scholar 

  48. Ishida N, Ito M, Yoshioka S, Sun-Wada GH, Kawakita M (1998) Functional expression of human golgi CMP-sialic acid transporter in the golgi complex of a transporter-deficient Chinese hamster ovary cell mutant. J Biochem 124(1):171–178

    Article  CAS  Google Scholar 

  49. Luhn K, Wild MK, Eckhardt M, Gerardy-Schahn R, Vestweber D (2001) The gene defective in leukocyte adhesion deficiency II encodes a putative GDP-fucose transporter. Nat Genet 28(1):69–72

    CAS  Google Scholar 

  50. Lubke T, Marquardt T, Etzioni A, Hartmann E, von Figura K, Korner C (2001) Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency. Nat Genet 28(1):73–76

    CAS  Google Scholar 

  51. Moriwaki K, Noda K, Nakagawa T, Asahi M, Yoshihara H, Taniguchi N, Hayashi N, Miyoshi E (2007) A high expression of GDP-fucose transporter in hepatocellular carcinoma is a key factor for increases in fucosylation. Glycobiology 17(12):1311–1320

    Article  CAS  Google Scholar 

  52. Liu L, Xu YX, Hirschberg CB (2010) The role of nucleotide sugar transporters in development of eukaryotes. Semin Cell Dev Biol 21(6):600–608

    Article  Google Scholar 

  53. Aoki K, Ishida N, Kawakita M (2001) Substrate recognition by UDP-galactose and CMP-sialic acid transporters. Different sets of transmembrane helices are utilized for the specific recognition of UDP-galactose and CMP-sialic acid. J Biol Chem 276(24):21555–21561

    Article  CAS  Google Scholar 

  54. Aoki K, Ishida N, Kawakita M (2003) Substrate recognition by nucleotide sugar transporters: further characterization of substrate recognition regions by analyses of UDP-galactose/CMP-sialic acid transporter chimeras and biochemical analysis of the substrate specificity of parental and chimeric transporters. J Biol Chem 278(25):22887–22893

    Article  CAS  Google Scholar 

  55. Takeshima-Futagami T, Sakaguchi M, Uehara E, Aoki K, Ishida N, Sanai Y, Sugahara Y, Kawakita M (2012) Amino acid residues important for CMP-sialic acid recognition by the CMP-sialic acid transporter: analysis of the substrate specificity of UDP-galactose/CMP-sialic acid transporter chimeras. Glycobiology. doi:10.1093/glycob/cws116

    Google Scholar 

  56. Commins SP, Platts-Mills TA (2010) Allergenicity of carbohydrates and their role in anaphylactic events. Curr Allergy Asthma Rep 10(1):29–33

    Article  CAS  Google Scholar 

  57. Chung CH, Mirakhur B, Chan E, Le QT, Berlin J, Morse M, Murphy BA, Satinover SM, Hosen J, Mauro D, Slebos RJ, Zhou Q, Gold D, Hatley T, Hicklin DJ, Platts-Mills TA (2008) Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med 358(11):1109–1117

    Article  CAS  Google Scholar 

  58. Lingg N, Zhang P, Song Z, Bardor M (2012) The sweet tooth of biopharmaceuticals: Importance of recombinant protein glycosylation analysis. Biotechnol J. doi: 10.1002/biot.201200078

  59. Ho SC, Bardor M, Mariati FH, Tong YW, Song Z, Yap MG, Yang Y (2012) IRES-mediated Tricistronic vectors for enhancing generation of high monoclonal antibody expressing CHO cell lines. J Biotechnol 157(1):130–139

    Article  CAS  Google Scholar 

  60. Junttila TT, Parsons K, Olsson C, Lu Y, Xin Y, Theriault J, Crocker L, Pabonan O, Baginski T, Meng G, Totpal K, Kelley RF, Sliwkowski MX (2010) Superior in vivo efficacy of afucosylated trastuzumab in the treatment of HER2-amplified breast cancer. Cancer Res 70(11):4481–4489

    Article  CAS  Google Scholar 

  61. Raju TS (2008) Terminal sugars of Fc glycans influence antibody effector functions of IgGs. Curr Opin Immunol 20(4):471–478

    Article  CAS  Google Scholar 

  62. Shields RL, Lai J, Keck R, O’Connell LY, Hong K, Meng YG, Weikert SHA, Presta LG (2002) Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fc gamma RIII and antibody-dependent cellular toxicity. J Biol Chem 277(30):26733–26740

    Article  CAS  Google Scholar 

  63. Peipp M, Lammerts van Bueren JJ, Schneider-Merck T, Bleeker WWK, Dechant M, Beyer T, Repp R, van Berkel PHC, Vink T, van de Winkel JGJ, Parren PWHI, Valerius T (2008) Antibody fucosylation differentially impacts cytotoxicity mediated by NK and PMN effector cells. Blood 112(6):2390–2399

    Article  CAS  Google Scholar 

  64. Niwa R, Shoji-Hosaka E, Sakurada M, Shinkawa T, Uchida K, Nakamura K, Matsushima K, Ueda R, Hanai N, Shitara K (2004) Defucosylated chimeric anti-CC chemokine receptor 4 IgG1 with enhanced antibody-dependent cellular cytotoxicity shows potent therapeutic activity to T-cell leukemia and lymphoma. Cancer Res 64(6):2127–2133

    Article  CAS  Google Scholar 

  65. Suzuki E, Niwa R, Saji S, Muta M, Hirose M, Iida S, Shiotsu Y, Satoh M, Shitara K, Kondo M, Toi M (2007) A nonfucosylated anti-HER2 antibody augments antibody-dependent cellular cytotoxicity in breast cancer patients. Clin Cancer Res 13(6):1875–1882

    Article  CAS  Google Scholar 

  66. Cardarelli PM, Moldovan-Loomis MC, Preston B, Black A, Passmore D, Chen TH, Chen S, Liu J, Kuhne MR, Srinivasan M, Assad A, Witte A, Graziano RF, King DJ (2009) In vitro and in vivo characterization of MDX-1401 for therapy of malignant lymphoma. Clin Cancer Res 15(10):3376–3383

    Article  CAS  Google Scholar 

  67. Matsumiya S, Yamaguchi Y, Saito J, Nagano M, Sasakawa H, Otaki S, Satoh M, Shitara K, Kato K (2007) Structural comparison of fucosylated and nonfucosylated Fc fragments of human immunoglobulin G1. J Mol Biol 368(3):767–779

    Article  CAS  Google Scholar 

  68. Radaev S, Sun P (2002) Recognition of immunoglobulins by Fcgamma receptors. Mol Immunol 38(14):1073–1083

    Article  CAS  Google Scholar 

  69. Imai-Nishiya H, Mori K, Inoue M, Wakitani M, Iida S, Shitara K, Satoh M (2007) Double knockdown of alpha1,6-fucosyltransferase (FUT8) and GDP-mannose 4,6-dehydratase (GMD) in antibody-producing cells: a new strategy for generating fully non-fucosylated therapeutic antibodies with enhanced ADCC. BMC Biotechnol 7:84

    Article  Google Scholar 

  70. Yamane-Ohnuki N, Kinoshita S, Inoue-Urakubo M, Kusunoki M, Iida S, Nakano R, Wakitani M, Niwa R, Sakurada M, Uchida K, Shitara K, Satoh M (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

    Article  CAS  Google Scholar 

  71. Kanda Y, Imai-Nishiya H, Kuni-Kamochi R, Mori K, Inoue M, Kitajima-Miyama K, Okazaki A, Iida S, Shitara K, Satoh M (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

    Article  CAS  Google Scholar 

  72. Malphettes L, Freyvert Y, Chang J, Liu PQ, Chan E, Miller JC, Zhou Z, Nguyen T, Tsai C, Snowden AW, Collingwood TN, Gregory PD, Cost GJ (2010) Highly efficient deletion of FUT8 in CHO cell lines using zinc-finger nucleases yields cells that produce completely nonfucosylated antibodies. Biotechnol Bioeng 106(5):774–783

    Article  CAS  Google Scholar 

  73. Ishiguro T, Kawai S, Habu K, Sugimoto M, Shiraiwa H, Iijima S, Ozaki S, Matsumoto T, Yamada-Okabe H (2010) A defucosylated anti-CD317 antibody exhibited enhanced antibody-dependent cellular cytotoxicity against primary myeloma cells in the presence of effectors from patients. Cancer Sci 101(10):2227–2233

    Article  CAS  Google Scholar 

  74. Anthony RM, Nimmerjahn F, Ashline DJ, Reinhold VN, Paulson JC, Ravetch JV (2008) Recapitulation of IVIG anti-inflammatory activity with a recombinant IgG Fc. Science 320(5874):373–376

    Article  CAS  Google Scholar 

  75. Kaneko Y, Nimmerjahn F, Ravetch JV (2006) Anti-inflammatory activity of immunoglobulin G resulting from Fc sialylation. Science 313(5787):670–673

    Article  CAS  Google Scholar 

  76. Leader B, Baca QJ, Golan DE (2008) Protein therapeutics: a summary and pharmacological classification. Nat Rev Drug Discov 7(1):21–39

    Article  CAS  Google Scholar 

  77. Van Hall EV, Vaitukaitis JL, Ross GT, Hickman JW, Ashwell G (1971) Effects of progressive desialylation on the rate of disappearance of immunoreactive HCG from plasma in rats. Endocrinology 89(1):11–15

    Article  Google Scholar 

  78. Grewal PK (2010) The Ashwell-Morell receptor. Methods Enzymol 479:223–241

    Article  CAS  Google Scholar 

  79. Fukuda MN, Sasaki H, Lopez L, Fukuda M (1989) Survival of recombinant erythropoietin in the circulation: the role of carbohydrates. Blood 73(1):84–89

    CAS  Google Scholar 

  80. Egrie JC, Browne JK (2001) Development and characterization of novel erythropoiesis stimulating protein (NESP). Br J Cancer 84(Suppl 1):3–10

    Article  CAS  Google Scholar 

  81. Wong NS, Yap MG, Wang DI (2006) Enhancing recombinant glycoprotein sialylation through CMP-sialic acid transporter over expression in Chinese hamster ovary cells. Biotechnol Bioeng 93(5):1005–1016

    Article  CAS  Google Scholar 

  82. Wang Z, Park JH, Park HH, Tan W, Park TH (2011) Enhancement of recombinant human EPO production and sialylation in Chinese hamster ovary cells through Bombyx mori 30Kc19 gene expression. Biotechnol Bioeng 108(7):1634–1642

    Article  CAS  Google Scholar 

  83. Chee Furng Wong D, Tin Kam Wong K, Tang Goh L, Kiat Heng C, Gek Sim Yap M (2005) Impact of dynamic online fed-batch strategies on metabolism, productivity and N-glycosylation quality in CHO cell cultures. Biotechnol Bioeng 89(2):164–177

    Article  Google Scholar 

  84. Fukuta K, Yokomatsu T, Abe R, Asanagi M, Makino T (2000) Genetic engineering of CHO cells producing human interferon-gamma by transfection of sialyltransferases. Glycoconj J 17(12):895–904

    Article  CAS  Google Scholar 

  85. Berg-Fussman A, Grace ME, Ioannou Y, Grabowski GA (1993) Human acid beta-glucosidase. N-glycosylation site occupancy and the effect of glycosylation on enzymatic activity. J Biol Chem 268(20):14861–14866

    CAS  Google Scholar 

  86. Pastores GM (2010) Recombinant glucocerebrosidase (imiglucerase) as a therapy for Gaucher disease. BioDrugs 24(1):41–47

    Article  CAS  Google Scholar 

  87. Brumshtein B, Salinas P, Peterson B, Chan V, Silman I, Sussman JL, Savickas PJ, Robinson GS, Futerman AH (2010) Characterization of gene-activated human acid-beta-glucosidase: crystal structure, glycan composition, and internalization into macrophages. Glycobiology 20(1):24–32

    Article  CAS  Google Scholar 

  88. He X, Galpin JD, Tropak MB, Mahuran D, Haselhorst T, von Itzstein M, Kolarich D, Packer NH, Miao Y, Jiang L, Grabowski GA, Clarke LA, Kermode AR (2012) Production of active human glucocerebrosidase in seeds of Arabidopsis thaliana complex-glycan-deficient (cgl) plants. Glycobiology 22(4):492–503

    Article  CAS  Google Scholar 

  89. Pastores GM (2010) Velaglucerase alfa, a human recombinant glucocerebrosidase enzyme replacement therapy for type 1 Gaucher disease. Curr Opin Investig Drugs 11(4):472–478

    CAS  Google Scholar 

  90. Shaaltiel Y, Bartfeld D, Hashmueli S, Baum G, Brill-Almon E, Galili G, Dym O, Boldin-Adamsky SA, Silman I, Sussman JL, Futerman AH, Aviezer D (2007) Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher’s disease using a plant cell system. Plant Biotechnol J 5(5):579–590

    Article  CAS  Google Scholar 

  91. Sinclair G, Pfeifer TA, Grigliatti TA, Choy FY (2006) Secretion of human glucocerebrosidase from stable transformed insect cells using native signal sequences. Biochem Cell Biol 84(2):148–156

    Article  CAS  Google Scholar 

  92. Zimran A, Brill-Almon E, Chertkoff R, Petakov M, Blanco-Favela F, Munoz ET, Solorio-Meza SE, Amato D, Duran G, Giona F, Heitner R, Rosenbaum H, Giraldo P, Mehta A, Park G, Phillips M, Elstein D, Altarescu G, Szleifer M, Hashmueli S, Aviezer D (2011) Pivotal trial with plant cell-expressed recombinant glucocerebrosidase, taliglucerase alfa, a novel enzyme replacement therapy for Gaucher disease. Blood 118(22):5767–5773

    Article  CAS  Google Scholar 

  93. Bardor M, Faveeuw C, Fitchette AC, Gilbert D, Galas L, Trottein F, Faye L, Lerouge P (2003) Immunoreactivity in mammals of two typical plant glyco-epitopes, core alpha(1,3)-fucose and core xylose. Glycobiology 13(6):427–434

    Article  CAS  Google Scholar 

  94. Rhee DK, Marcelino J, Baker M, Gong Y, Smits P, Lefebvre V, Jay GD, Stewart M, Wang H, Warman ML, Carpten JD (2005) The secreted glycoprotein lubricin protects cartilage surfaces and inhibits synovial cell overgrowth. J Clin Invest 115(3):622–631

    CAS  Google Scholar 

  95. Jay GD, Harris DA, Cha CJ (2001) Boundary lubrication by lubricin is mediated by O-linked beta(1–3)Gal-GalNAc oligosaccharides. Glycoconj J 18(10):807–815

    Article  CAS  Google Scholar 

  96. Estrella RP, Whitelock JM, Packer NH, Karlsson NG (2010) The glycosylation of human synovial lubricin: implications for its role in inflammation. Biochem J 429(2):359–367

    Article  CAS  Google Scholar 

  97. Wong AW, Baginski TK, Reilly DE (2010) Enhancement of DNA uptake in FUT8-deleted CHO cells for transient production of afucosylated antibodies. Biotechnol Bioeng 106(5):751–763

    Article  CAS  Google Scholar 

  98. Xu YX, Liu L, Caffaro CE, Hirschberg CB (2010) Inhibition of Golgi apparatus glycosylation causes endoplasmic reticulum stress and decreased protein synthesis. J Biol Chem 285(32):24600–24608

    Article  CAS  Google Scholar 

  99. Xu X, Nagarajan H, Lewis NE, Pan S, Cai Z, Liu X, Chen W, Xie M, Wang W, Hammond S, Andersen MR, Neff N, Passarelli B, Koh W, Fan HC, Wang J, Gui Y, Lee KH, Betenbaugh MJ, Quake SR, Famili I, Palsson BO (2011) The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line. Nat Biotechnol 29(8):735–741

    Article  CAS  Google Scholar 

  100. Davies SL, Lovelady CS, Grainger RK, Racher AJ, Young RJ, James DC (2012) Functional heterogeneity and heritability in CHO cell populations. Biotechnol Bioeng. doi:10.1002/bit.24621

    Google Scholar 

Download references

Acknowledgments

The authors would like to thank Ms. Natasha Pereira for critical review of the manuscript. This work is supported by the Biomedical Research Council, Agency for Science, Technology and Research (A*STAR), Singapore.

Author information

Authors and Affiliations

  1. Bioprocessing Technology Institute, Agency for Science, Technology and Research (A*STAR), 20 Biopolis Way, #06-01 Centros, Singapore, 138668, Singapore

    Peiqing Zhang, Kah Fai Chan, Ryan Haryadi, Muriel Bardor & Zhiwei Song

Authors
  1. Peiqing Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kah Fai Chan
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ryan Haryadi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Muriel Bardor
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Zhiwei Song
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. School of Life Sciences & Biotechnology, Bio-Building #3-311, Shanghai Jiao Tong University, Dong-Chuan Road 800, Shanghai, 200240, China, People's Republic

    Jian-Jiang Zhong

Rights and permissions

Reprints and permissions

Copyright information

© 2012 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Zhang, P., Chan, K.F., Haryadi, R., Bardor, M., Song, Z. (2012). CHO Glycosylation Mutants as Potential Host Cells to Produce Therapeutic Proteins with Enhanced Efficacy. In: Zhong, JJ. (eds) Future Trends in Biotechnology. Advances in Biochemical Engineering/Biotechnology, vol 131. Springer, Berlin, Heidelberg. https://doi.org/10.1007/10_2012_163

Download citation

Publish with us

Policies and ethics

Search

Navigation