Strategies for engineering protein N-glycosylation pathways in mammalian cells

Glyco-Engineering: Methods and Protocols

Volumn , Issue , 2015, Pages 287-305

  Wang, Qiong ^a   Stuczynski, Mark ^a   Gao, Yuan ^a   Betenbaugh, Michael J ^a  

^a Johns Hopkins University   (United States)

Author keywords

Cell culture conditions; Fucosylation; Glyco engineering; Mammalian expression systems; N linked glycosylation; Sialylation

Indexed keywords

POLYSACCHARIDE; PROTEIN;

ANIMAL; BIOTECHNOLOGY; CHO CELL LINE; CRICETULUS; GENETIC ENGINEERING; GENETICS; GLYCOSYLATION; HUMAN; MAMMAL; PROCEDURES;

ANIMALS; BIOTECHNOLOGY; CHO CELLS; CRICETULUS; GENETIC ENGINEERING; GLYCOSYLATION; HUMANS; MAMMALS; POLYSACCHARIDES; PROTEINS;

EID: 84957360477     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4939-2760-9_20     Document Type: Chapter

References (103)

1. Arnold JN, Wormald MR, Sim RB et al (2007) The impact of glycosylation on the biological function and structure of human immunoglobulins. Annu Rev Immunol 25:21-50.
2. Li H, d'Anjou M (2009) Pharmacological significance of glycosylation in therapeutic proteins. Curr Opin Biotechnol 20:678-684.
3. Andersen DC, Reilly DE (2004) Production technologies for monoclonal antibodies and their fragments. Curr Opin Biotechnol 15:456-462.
4. Walsh G (2010) Biopharmaceutical benchmarks. Nat Biotechnol 28:917-924.
5. Wurm FM (2004) Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 22:1393-1398.
6. Betenbaugh MJ, Tomiya N, Narang S et al (2004) Biosynthesis of human-type N-glycans in heterologous systems. Curr Opin Struct Biol 14:601-606.
7. Jayapal KR, Wlaschin KF, Hu WS et al (2007) Recombinant protein therapeutics from CHO cells-20 years and counting. Chem Eng Prog 103:40-47.
8. Butler M (2005) Animal cell cultures, recent achievements and perspectives in the production of biopharmaceuticals. Appl Microbiol Biotechnol 68:283-291.
9. Durocher Y, Butler M (2009) Expression systems for therapeutic glycoprotein production. Curr Opin Biotechnol 20:700-707.
10. Hossler P, Khattak SF, Li ZJ (2009) Optimal and consistent protein glycosylation in mammalian cell culture. Glycobiology 19:936-949.
11. Stacey G, Davis J (2007) In: Stacey G, Davis J (Eds). Medicines from animal cell culture, vol. XVI. Wiley, Chichester. pp. 672.
12. Jefferis R (2005) Glycosylation of natural and recombinant antibody molecules. Adv Exp Med Biol 564:143-148.
13. Jenkins N, Curling EMA (1994) Glycosylation of recombinant proteins-problems and prospects. Enzyme Microb Technol 16:354-364.
14. Umana P, Jean-Mairet J, Moudry R et al (1999) Engineered glycoforms of an antineuroblastoma IgG1 with optimized antibodydependent cellular cytotoxic activity. Nat Biotechnol 17:176-180.
15. Varki A (2001) Loss of N-glycolylneuraminic acid in humans, mechanisms, consequences, and implications for hominid evolution. Am J Phys Anthropol 33:54-69.
16. Tangvoranuntakul P, Gagneux P, Diaz S et al (2003) Human uptake and incorporation of an immunogenic non-human dietary sialic acid. Proc Natl Acad Sci U S A 100:12045-12050.
17. Bardor M, Nguyen DH, Diaz S et al (2005) Mechanism of uptake and incorporation of the non-human sialic acid N-glycolylneuraminic acid into human cells. J Biol Chem 280:4228-4237.
18. Padler-Karavani V, Hurtado-Ziola N, Pu MY et al (2011) Human xeno-autoantibodies against a non-human sialic acid serve as novel serum biomarkers and immunotherapeutics in cancer. Cancer Res 71:3352-3363.
19. Noguchi A, Mukuria CJ, 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 Tokyo 117:59-62.
20. Birch JR, Racher AJ (2006) Antibody production. Adv Drug Deliv Rev 58:671-685.
21. Zhang M, Koskie K, Ross JS et al (2010) Enhancing glycoprotein sialylation by targeted gene silencing in mammalian cells. Biotechnol Bioeng 105:1094-1105.
22. Chen PF, Harcum SW (2006) Effects of elevated ammonium on glycosylation gene expression in CHO cells. Metab Eng 8:123-132.
23. Galili U, Rachmilewitz EA, Peleg A et al (1984) Unique natural human-Igg antibody with anti-alpha-galactosyl specificity. J Exp Med 160:1519-1531.
24. Chung CH, Mirakhur B, Chan E et al (2008) Cetuximab-induced anaphylaxis and IgE specific for galactose-alpha-1,3-galactose. N Engl J Med 358:1109-1117.
25. Beck A, Wagner-Rousset E, Bussat MC et al (2008) Trends in glycosylation, glycoanalysis and glycoengineering of therapeutic antibodies and Fc-fusion proteins. Curr Pharma Biotechnol 9:482-501.
26. Padler-Karavani V, Yu H, Cao HZ et al (2008) Diversity in specificity, abundance, and composition of anti-Neu5Gc antibodies in normal humans: Potential implications for disease. Glycobiology 18:818-830.
27. Sheeley DM, Reinhold VN (1997) The detailed structural characterization of N-linked oligosaccharides using a quadrupole ion trap mass spectrometer. Glycobiology 7:38.
28. Dingermann T (2008) Recombinant therapeutic proteins: production platforms and challenges. Biotechnol J 3:90-97.
29. Krambeck FJ, Betenbaugh MJ (2005) A mathematical model of N-linked glycosylation. Biotechnol Bioeng 92:711-728.
30. Wang LX, Lomino JV (2012) Emerging technologies for making glycan-defined glycoproteins. ACS Chem Biol 7:110-122.
31. Angata T, Varki A (2002) Chemical diversity in the sialic acids and related alpha-keto acids:An evolutionary perspective. Chem Rev 102:439-469.
32. Ashwell G, Morell A (1974) The dual role of sialic acid in the hepatic recognition and catabolism of serum glycoproteins. Biochem Soc Symp 40:117-124.
33. Ngantung FA, Miller PG, Brushett FR et al (2006) RNA interference of sialidase improves glycoprotein sialic acid content consistency. Biotechnol Bioeng 95:106-119.
34. Schauer R (2004) Sialic acids: fascinating sugars in higher animals and man. Zoology 107:49-64.
35. Bragonzi A, Distefano G, Buckberry LD et al (2000) A new Chinese hamster ovary cell line expressing alpha2,6-sialyltransferase used as universal host for the production of humanlike sialylated recombinant glycoproteins. Biochim Biophys Acta 1474:273-282.
36. Gu X, Wang DI (1998) Improvement of interferon-gamma sialylation in Chinese hamster ovary cell culture by feeding of N-acetylmannosamine. Biotechnol Bioeng 58:642-648.
37. Zhang P, Tan DL, Heng D et al (2010) A functional analysis of N-glycosylation-related genes on sialylation of recombinant erythropoietin in six commonly used mammalian cell lines. Metab Eng 12:526-536.
38. Minch SL, Kallio PT, Bailey JE (1995) Tissue plasminogen activator coexpressed in Chinese hamster ovary cells with alpha(2,6)-sialyltransferase contains NeuAc alpha(2,6)Gal beta(1,4)Glc-N-AcR linkages. Biotechnol Prog 11:348-351.
39. Fukuta K, Abe R, Yokomatsu T et al (2000) Remodeling of sugar chain structures of human interferon-gamma. Glycobiology 10:421-430.
40. Jassal R, Jenkins N, Charlwood J et al (2001) Sialylation of human IgG-Fc carbohydrate by transfected rat alpha2,6-sialyltransferase. Biochem Biophys Res Commun 286:243-249.
41. Weikert S, Papac D, Briggs J et al (1999) Engineering Chinese hamster ovary cells to maximize sialic acid content of recombinant glycoproteins. Nat Biotechnol 17:1116-1121.
42. Jeong YT, Choi O, Lim HR et al (2008) Enhanced sialylation of recombinant erythropoietin in CHO cells by human glycosyltransferase expression. J Microbiol Biotechnol 18:1945-1952.
43. Munster-Kuhnel AK, Tiralongo J, Krapp S et al (2004) Structure and function of vertebrate CMP-sialic acid synthetases. Glycobiology 14:43R-51R.
44. Hooker AD, Green NH, Baines AJ et al (1999) Constraints on the transport and glycosylation of recombinant IFN-gamma in Chinese hamster ovary and insect cells. Biotechnol Bioeng 63:559-572.
45. Lawrence SM, Huddleston KA, Tomiya N et al (2001) Cloning and expression of human sialic acid pathway genes to generate CMPsialic acids in insect cells. Glycoconj J 18:205-213.
46. 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 93:1005-1016.
47. Jeong YT, Choi O, Son YD et al (2009) Enhanced sialylation of recombinant erythropoietin in genetically engineered Chinesehamster ovary cells. Biotechnol Appl Biochem 52:283-291.
48. Son YD, Jeong YT, Park SY et al (2011) Enhanced sialylation of recombinant human erythropoietin in Chinese hamster ovary cells by combinatorial engineering of selected genes. Glycobiology 21:1019-1028.
49. Monti E, Preti A, Venerando B et al (2002) Recent development in mammalian sialidase molecular biology. Neurochem Res 27:649-663.
50. de Geest N, Bonten E, Mann L et al (2002) Systemic and neurologic abnormalities distinguish the lysosomal disorders sialidosis and galactosialidosis in mice. Human Mol Genet 11:1455-1464.
51. Hinek A, Pshezhetsky AV, von Itzstein M et al (2006) Lysosomal sialidase (neuraminidase-1) is targeted to the cell surface in a multiprotein complex that facilitates elastic fiber assembly. J Biol Chem 281:3698-3710.
52. Kakugawa Y, Wada T, Yamaguchi K et al (2002) Up-regulation of plasma membraneassociated ganglioside sialidase (Neu3) in human colon cancer and its involvement in apoptosis suppression. Proc Natl Acad Sci U S A 99:10718-10723.
53. Seyrantepe V, Landry K, Trudel S et al (2004) Neu4, a novel human lysosomal lumen sialidase, confers normal phenotype to sialidosis and galactosialidosis cells. J Biol Chem 279:37021-37029.
54. Tringali C, Papini N, Fusi P et al (2004) Properties of recombinant human cytosolic sialidase HsNEU2. The enzyme hydrolyzes monomerically dispersed GM1 ganglioside molecules. J Biol Chem 279:3169-3179.
55. Ferrari J, Gunson J, Lofgren J et al (1998) Chinese hamster ovary cells with constitutively expressed sialidase antisense RNA produce recombinant DNase in batch culture with increased sialic acid. Biotechnol Bioeng 60:589-595.
56. Clynes RA, Towers TL, Presta LG et al (2000) Inhibitory Fc receptors modulate in vivo cytotoxicity against tumor targets. Nat Med 6:443-446.
57. Matsumiya S, Yamaguchi Y, Saito J et al (2007) Structural comparison of fucosylated and nonfucosylated Fc fragments of human immunoglobulin G1. J Mol Biol 368:767-779.
58. Kanda Y, Yamada T, Mori K et al (2007) Comparison of biological activity among nonfucosylated therapeutic IgG1 antibodies with three different N-linked Fe oligosaccharides:the high-mannose, hybrid, and complex types. Glycobiology 17:104-118.
59. Iida S, Misaka H, Inoue M et al (2006) Nonfucosylated therapeutic IgG1 antibody can evade the inhibitory effect of serum immunoglobulin g on antibody-dependent cellular cytotoxicity through its high binding to Fc gamma RIIIa. Clin Cancer Res 12:2879-2887.
60. Miyoshi E, Noda K, Yamaguchi Y et al (1999) The alpha 1-6-fucosyltransferase gene and its biological significance. Bba-Gen Subjects 1473:9-20.
61. Mori K, Kuni-Karnochi R, Yarnane-Ohnuki N et al (2004) Engineering Chinese hamster ovary cells to maximize effector function of produced antibodies using FUT8 siRNA. Biotechnol Bioeng 88:901-908.
62. 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 87:614-622.
63. Ma B, Simala-Grant JL, Taylor DE (2006) Fucosylation in prokaryotes and eukaryotes. Glycobiology 16:158R-184R.
64. Mori K, Iida S, Yamane-Ohnuki N et al (2007) Non-fucosylated therapeutic antibodies, the next generation of therapeutic antibodies. Cytotechnology 55:109-114.
65. Urnov FD, Rebar EJ, Holmes MC et al (2010) Genome editing with engineered zinc finger nucleases. Nat Rev Genet 11:636-646.
66. Cristea S, Freyvert Y, Santiago Y et al (2013) In vivo cleavage of transgene donors promotes nuclease-mediated targeted integration. Biotechnol Bioeng 110:871-880.
67. Shinkawa T, Nakamura K, Yamane N et al (2003) The absence of fucose but not thepresence 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 278:3466-3473.
68. Pastuszak I, Ketchum C, Hermanson G et al (1998) GDP-L-fucose pyrophosphorylase. Purification, cDNA cloning, and properties of the enzyme. J Biol Chem 273:30165-30174.
69. 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 130:300-310.
70. Omasa T, Tanaka R, Doi T et al (2008) Decrease in antithrombin III fucosylation by expressing GDP-fucose transporter siRNA in Chinese hamster ovary cells. J Biosci Bioeng 106:168-173.
71. Imai-Nishiya H, Mori K, Inoue M et al (2007) Double knockdown of alpha1,6- fucosyltransferase (FUT8) and GDP-mannose 4,6-dehydratase (GMD) in antibodyproducing cells: a new strategy for generating fully non-fucosylated therapeutic antibodies with enhanced ADCC. BMC Biotechnol 7:84.
72. Ripka J, Adamany A, Stanley P (1986) Two Chinese hamster ovary glycosylation mutants affected in the conversion of GDP-mannose to GDP-fucose. Arch Biochem Biophys 249:533-545.
73. Shields RL, Lai J, Keck R et al (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 277:26733-26740.
74. Yamane-Ohnuki N, Satoh M (2009) Production of therapeutic antibodies with controlled fucosylation. MAbs 1:230-236.
75. Schuster M, Umana P, Ferrara C et al (2005) Improved effector functions of a therapeutic monoclonal Lewis Y-specific antibody by glycoform engineering. Cancer Res 65:7934-7941.
76. Davies J, Jiang L, Pan LZ et al (2001) Expression of GnTIII in a recombinant anti-CD20 CHO production cell line: expression of antibodies with altered glycoforms leads to an increase in ADCC through higher affinity for FC gamma RIII. Biotechnol Bioeng 74:288-294.
77. 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 93:851-861.
78. Ferrara C, Stuart F, Sondermann P et al (2006) The carbohydrate at Fc gamma RIIIa Asn-162. An element required for high affinity binding to non-fucosylated IgG glycoforms. J Biol Chem 281:5032-5036.
79. Castilho A, Gattinger P, Grass J et al (2011) N-glycosylation engineering of plants for the biosynthesis of glycoproteins with bisected and branched complex N-glycans. Glycobiology 21:813-823.
80. Zhao Y, Sato Y, Isaji T et al (2008) Branched N-glycans regulate the biological functions of integrins and cadherins. FEBS J 275:1939-1948.
81. Demetriou M, Granovsky M, Quaggin S et al (2001) Negative regulation of T-cell activation and autoimmunity by Mgat5 N-glycosylation. Nature 409:733-739.
82. Lau KS, Dennis JW (2008) N-Glycans in cancer progression. Glycobiology 18:750-760.
83. Fukuta K, Yokomatsu T, Abe R et al (2000) Genetic engineering of CHO cells producing human interferon-gamma by transfection of sialyltransferases. Glycoconj J 17:895-904.
84. Elliott S, Lorenzini T, Asher S et al (2003) Enhancement of therapeutic protein in vivo activities through glycoengineering. Nat Biotechnol 21:414-421.
85. Egrie JC, Dwyer E, Browne JK et al (2003) Darbepoetin alfa has a longer circulating halflife and greater in vivo potency than recombinant human erythropoietin. Exp Hematol 31:290-299.
86. Egrie JC, Browne JK (2001) Development and characterization of novel erythropoiesis stimulating protein (NESP). Nephrol Dial Transplant 16:3-13.
87. Macdougall IC (1999) The role of ACE inhibitors and angiotensin II receptor blockers in the response to epoetin. Nephrol Dial Transplant 14:1836-1841.
88. Perlman S, van den Hazel B, Christiansen J et al (2003) Glycosylation of an N-terminal extension prolongs the half-life and increases the in vivo activity of follicle stimulating hormone. J Clin Endocrinol Metabol 88:3227-3235.
89. Stork R, Zettlitz KA, Muller D et al (2008) N-glycosylation as novel strategy to improve pharmacokinetic properties of bispecific single- chain diabodies. J Biol Chem 283:7804-7812.
90. Kronman C, Velan B, Marcus D et al (1995) Involvement of oligomerization, N-glycosylation and sialylation in the clearance of cholinesterases from the circulation. Biochem J 311:959-967.
91. Chitlaru T, Kronman C, Velan B et al (2002) Overloading and removal of N-glycosylation targets on human acetylcholinesterase: effects on glycan composition and circulatory residence time. Biochem J 363:619-631.
92. Kronman C, Chitlaru T, Elhanany E et al (2000) Hierarchy of post-translational modifications involved in the circulatory longevity of glycoproteins. Demonstration of concerted contributions of glycan sialylation and subunit assembly to the pharmacokinetic behavior of bovine acetylcholinesterase. J Biol Chem 275:29488-29502.
93. Chitlaru T, Kronman C, Velan B et al (2001) Effect of human acetylcholinesterase subunit assembly on its circulatory residence. Biochem J 354:613-625.
94. Gawlitzek M, Valley U, Nimtz M et al (1995) Characterization of changes in the glycosylation pattern of recombinant proteins from BHK-21 cells due to different culture conditions. J Biotechnol 42:117-131.
95. Patel TP, Parekh RB, Moellering BJ et al (1992) Different culture methods lead to differences in glycosylation of a murine IgG monoclonal antibody. Biochem J 285:839-845.
96. Yang M, Butler M (2002) Effects of ammonia and glucosamine on the heterogeneity of erythropoietin glycoforms. Biotechnol Prog 18:129-138.
97. Zhao FQ, Keating AF (2007) Functional properties and genomics of glucose transporters. Curr Genomics 8:113-128.
98. Wong DCF, Wong KTK, Goh LT et al (2005) Impact of dynamic online fed-batch strategies on metabolism, productivity and N-glycosylation quality in CHO cell cultures. Biotechnol Bioeng 89:164-177.
99. Nyberg GB, Balcarcel RR, Follstad BD et al (1999) Metabolic effects on recombinant interferon-gamma glycosylation in continuous culture of Chinese hamster ovary cells. Biotechnol Bioeng 62:336-347.
100. Costa AR, Rodrigues ME, Henriques M et al (2014) Glycosylation: impact, control and improvement during therapeutic protein production. Crit Rev Biotechnol 34:281-299.
101. Bulter T, Lee SG, Wong WW et al (2004) Design of artificial cell-cell communication using gene and metabolic networks. Proc Natl Acad Sci U S A 101:2299-2304.
102. Kimura R, Miller WM (1999) Glycosylation of CHO-derived recombinant tPA produced under elevated pCO2. Biotechnol Prog 13:311-317.
103. Zanghi JA, Fussenegger M, Bailey JE (1999) Serum protects protein-free competent Chinese hamster ovary cells against apoptosis induced by nutrient deprivation in batch culture. Biotechnol Bioeng 64:108-119.