Molecular farming of human cytokines and blood products from plants: Challenges in biosynthesis and detection of plant-produced recombinant proteins

Biotechnology Journal

Volumn 9, Issue 1, 2014, Pages 39-50

  da Cunha, Nicolau B ^a   Vianna, Giovanni R ^a   da Almeida Lima, Thaina ^a   Rech, Elíbio ^a  

^a EMBRAPA RECURSOS GENÉTICOS E BIOTECNOLOGIA   (Brazil)

Author keywords

Cytokines; Glycoengineering; Molecular farming; Plant based production; Recombinant plasma proteins

Indexed keywords

CYTOKINES; FEASIBLE ALTERNATIVES; GLYCOENGINEERING; INDUSTRIAL PROTEINS; MAMMALIAN CELL CULTURE; MOLECULAR FARMING; PLASMA PROTEIN; THERAPEUTIC PROTEIN;

BIOCHEMISTRY; BIOSYNTHESIS; CELL CULTURE; INDUSTRIAL PLANTS; MOLECULES; PRODUCTION PLATFORMS;

RECOMBINANT PROTEINS;

ANTICOAGULANT AGENT; BLOOD CLOTTING FACTOR; ERYTHROPOIETIN; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; IMMUNOGLOBULIN; INFLUENZA VACCINE; PLASMA PROTEIN; RECOMBINANT ALPHA2B INTERFERON; RECOMBINANT CYTOKINE; RECOMBINANT SOMATOMEDIN C; SOMATOMEDIN C; TALIGLUCERASE ALFA; VEGETABLE PROTEIN;

ARTICLE; BIOSYNTHESIS; BLEEDING; BLOOD; CELL SUSPENSION; CYTOKINE PRODUCTION; GENE EXPRESSION SYSTEM; GENETIC RECOMBINATION; GLYCOSYLATION; GOOD MANUFACTURING PRACTICE; HUMAN; LARGE SCALE PRODUCTION; LEMNA MINOR; LEUKOCYTE; MAMMAL CELL; MOLECULAR FARMING; NONHUMAN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 3 CLINICAL TRIAL (TOPIC); PLANT PRODUCT; PLASMA; PLASTID GENOME; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN TARGETING; PROTOPLAST; RECOMBINANT DNA TECHNOLOGY; TRANSGENIC PLANT; TRANSIENT EXPRESSION;

MAMMALIA;

CYTOKINES; GLYCOENGINEERING; MOLECULAR FARMING; PLANT-BASED PRODUCTION; RECOMBINANT PLASMA PROTEINS;

BIOLOGICAL PRODUCTS; BLOOD PROTEINS; CYTOKINES; HUMANS; MOLECULAR FARMING; PLANTS, GENETICALLY MODIFIED; PROTEIN ENGINEERING; RECOMBINANT PROTEINS; TECHNOLOGY, PHARMACEUTICAL;

EID: 84891930928     PISSN: 18606768     EISSN: 18607314     Source Type: Journal    
DOI: 10.1002/biot.201300062     Document Type: Article

References (116)

1. Xu, J., Dolan, M. C., Medrano, G., Cramer, C. L., Weathers, P. J., Green factory: Plants as bioproduction platforms for recombinant proteins. Biotechnol. Adv. 2012, 30, 1171-1184.
2. Paul, M., Ma, J. K. C., Plant-made pharmaceuticals: Leading products and production platforms. Biotechnol. Appl. Biochem. 2011, 58, 58-67.
3. Paul, M., Dolleweerd, C. V., Drake, P. M. W., Reljic, R. et al., Molecular pharming: Future targets and aspirations. Hum. Vaccin. 2011, 7, 375-382.
4. Tiwari, S., Verma, P. C., Singh, P. K., Tuli, R., Plants as bioreactors for the production of vaccine antigens. Biotechnol. Adv. 2009, 27, 449-467.
5. Vianna, G. R., Cunha, N. B., Murad, A. M., Rech, E. L., Soybeans as bioreactors for biopharmaceuticals and industrial proteins. Genet. Mol. Res. 2011, 10, 1733-1752.
6. Tremblay, R., Wang, D., Jevnikar, A. M., Ma, S., Tobacco, a highly efficient green bioreactor for production of therapeutic proteins. Biotechnol. Adv. 2010, 28, 214-221.
7. Gleba, Y., Klimyuk, V., Marillonnet, S., Magnifection - A new platform for expressing recombinant vaccines in plants. Vaccine 2005, 23, 2042-2048.
8. Rech, E. L., Seeds, recombinant DNA and biodiversity. Seed Sci. Res. 2012, 22, S36-S44.
9. Ma, J. K. C., Drake, P. M. W., Christou, P., The production of recombinant pharmaceutical proteins in plants. Nat. Rev. Genet. 2003, 4, 794-805.
10. Davies, H. M., Commercialization of whole-plant systems for biomanufacturing of protein products: evolution and prospects. Plant Biotechnol. J. 2010, 8, 845-861.
11. Paul, M. J., Teh, A. Y., Twyman, R. M., Ma, J. K., Target product selection - where can Molecular Pharming make the difference? Curr. Pharm. Des. 2013, 8, 5478-85.
12. Shaaltiel, Y., Bartfeld, D., Hashmueli, S., Baum, G. et al., Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher's disease using a plant cell system. Plant Biotechnol. J. 2007, 5, 579-590.
13. Thalayasingam, N., Isaacs, J. D., Anti-TNF therapy. Best Pract. Res. Clin. Rheumatol. 2011, 25, 549-567.
14. Landry, N., Ward, B. J., Trépanier, S., Montomoli, E. et al., Preclinical and clinical development of plant-made virus-like particle vaccine against avian H5N1 influenza. PLoS One 2010, 5.
15. De Leede, L. G., Humphries, J. E., Bechet, A. C., Van Hoogdalem, E. J. et al., Novel controlled release Lemna-derived IFN-alpha2b (Locteron): pharmacokinetics, pharmacodynamics, and tolerability in a phase I clinical trial. J. Interferon Cytokine Res. 2008, 28, 113-122.
16. Sparrow, P. A., Irwin, J. A., Dale, P. J., Twyman, R. M., Ma, J. K., Pharma-Planta: road testing the developing regulatory guidelines for plant-made pharmaceuticals. Transgenic Res. 2007, 16, 147-161.
17. Obembe, O. O., Popoola, J. O., Leelavathi, S., Reddy, S. V., Advances in plant molecular farming. Biotechnol. Adv. 2011, 29, 210-222.
18. Burnouf, T., Recombinant plasma proteins. Vox Sang. 2011, 100, 68-83.
19. Pipe, S. W., Hemophilia: New Protein Therapeutics. Hematology Am. Soc. Hematol. Educ. Program. 2010, 2010, 203-209.
20. Pipe, S. W., The promise and challenges of bioengineered recombinant clotting factors. J. Thromb. Haemost. 2005, 3, 1692-1701.
21. Pipe, S. W., Recombinant clotting factors. Thromb. Haemost. 2008, 99, 840-850.
22. Farrugia, A., Robert, P., Plasma protein therapies: current and future perspectives. Best Pract. Res. Clin. Haematol. 2006, 19, 243-258.
23. Burnouf, T., Modern Plasma Fractionation. Transfus. Med. Rev. 2007, 21, 101-17.
24. Kurachi, K., Davie, E. W., Isolation and characterization of a cDNA coding for human factor IX. Proc. Natl. Acad. Sci. U S A. 1982, 79, 6461-6464.
25. Demain, A. L., Vaishnav, P., Production of recombinant proteins by microbes and higher organisms. Biotechnol. Adv. 2009, 27, 297-306.
26. Egelkrout, E., Rajan, V., Howard, J. A., Overproduction of recombinant proteins in plants. Plant Sci. 2012, 184, 83-101.
27. Grillberger, L., Kreil, T. R., Nasr, S., Reiter, M., Emerging trends in plasma-free manufacturing of recombinant protein therapeutics expressed in mammalian cells. Biotechnol. J. 2009, 4, 186-201.
28. Melnik, S., Stoger, E., Green Factories for Biopharmaceuticals. Curr. Med. Chem. 2013, 20, 1038-1046.
29. Xu, J., Ge, X., Dolan, M. C., Towards high-yield production of pharmaceutical proteins with plant cell suspension cultures. Biotechnol. Adv. 2011, 29, 278-299.
30. Streatfield, S. J., Approaches to achieve high-level heterologous protein production in plants. Plant Biotechnol. J. 2007, 5, 2-15.
31. Stoger, E., Sack, M., Perrin, Y., Vaquero, C. et al., Practical considerations for pharmaceutical antibody production in different crop systems. Mol. Breed. 2002, 9, 149-58.
32. Tayal, V., Kalra, B. S., Cytokines and anti-cytokines as therapeutics - an update. Eur. J. Pharmacol. 2008, 579, 1-12.
33. Cutler, A., Brombacher, F., Cytokine Therapy. Ann. N. Y, Acad. Sci. 2005, 1056, 16-29.
34. Snykers, S., Vanhaecke, T., Papeleu, P., Luttun, A. et al., Sequential Exposure to Cytokines Reflecting Embryogenesis: The Key for in vitro Differentiation of Adult Bone Marrow Stem Cells into Functional Hepatocyte-like Cells. Toxicol. Sci. 2006, 94, 330-341.
35. Kinoshita, T., Miyajima, A., Cytokine regulation of liver development. Biochim. Biophys. Acta. 2002, 1592, 303-312.
36. Sirko, A., Vanek, T., Góra-Sochacka, A., Redkiewicz, P., Recombinant Cytokines from Plants. Int. J. Mol. Sci. 2011, 12, 3536-3552.
37. Dinarello, C. A., Biologic basis for interleukin-1 in disease. Blood 1996, 87, 2095-2147.
38. Imaizumi, K., Nishikawa, S.-I., Tarui, H., Akuta, T., High-level expression and efficient one-step chromatographic purification of a soluble human leukemia inhibitory factor (LIF) in Escherichia coli. Protein Expr. Purif. 2013, 90, 20-26.
39. Xie, Y. F., Chen, H., Huang, B. R., Expression, purification and characterization of human IFN-1 in Pichia pastoris. J. Biotechnol. 2007, 129, 472-480.
40. Castilho, A., Neumann, L., Gattinger, P., Strasser, R. et al., Generation of Biologically Active Multi-Sialylated Recombinant Human EPOFc in Plants. PLoS One. 2013, 8.
41. Castilho, A., Steinkellner, H., Glyco-engineering in plants to produce human-like N-glycan structures. Biotechnol. J. 2012, 7, 1088-1098.
42. Gomord, V., Fitchette, A.-C., Menu-Bouaouiche, L., Saint-Jore-Dupas, C. et al., Plant-specific glycosylation patterns in the context of therapeutic protein production. Plant Biotechnol. J. 2010, 8, 564-587.
43. Gomord, V., Chamberlain, P., Jefferis, R., Faye, L., Biopharmaceutical production in plants: problems, solutions and opportunities. Trends Biotechnol. 2005, 23, 559-565.
44. Matsumoto, S., Ikura, K., Ueda, M., Sasaki, R., Characterization of a human glycoprotein (erythropoietin) produced in cultured tobacco cells. Plant Mol. Biol. 1995, 27, 1163-1172.
45. Jez, J., Castilho, A., Grass, J., Vorauer-Uhl, K. et al., Expression of functionally active sialylated human erythropoietin in plants. Biotechnol. J. 2013, 8, 371-382.
46. Tsuda, E., Goto, M., Murakami, A., Akai, K. et al., Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins. Biochemistry 1988, 27, 5646-5654.
47. Weise, A., Altmann, F., Rodriguez-Franco, M., Sjoberg, E. R. et al., High-level expression of secreted complex glycosylated recombinant human erythropoietin in the Physcomitrella Δ-fuc-t Δ-xyl-t mutant. Plant Biotechnol. J. 2007, 5, 389-401.
48. Matsumoto, S., Ishii, A., Ikura, K., Ueda, M., Sasaki, R., Expression of Human Erythropoietin in Cultured Tobacco Cells. Biosci. Biotechnol. Biochem. 1993, 57, 1249-1252.
49. Cheon, B., Kim, H., Oh, K., Bahn, S. et al., Overexpression of human erythropoietin (EPO) affects plant morphologies: retarded vegetative growth in tobacco and male sterility in tobacco and Arabidopsis. Transgenic Res. 2004, 13, 541-549.
50. Paulus, K. E., Mahler, V., Pabst, M., Kogel, K.-H. et al., Silencing ß1, 2-xylosyltransferase in transgenic tomato fruits reveals xylose as constitutive component of IgE binding epitopes. Front. Plant Sci. 2011, 2, 1-12.
51. Koprivova, A., Stemmer, C., Altmann, F., Hoffmann, A. et al., Targeted knockouts of Physcomitrella lacking plant-specific immunogenic N-glycans. Plant Biotechnol J. 2004, 2, 517-523.
52. Castilho, A., Gattinger, P., Grass, J., Jez, J. et al., N-Glycosylation engineering of plants for the biosynthesis of glycoproteins with bisected and branched complex N-glycans. Glycobiology. 2011, 21, 813-823.
53. Pessach, I., Shimoni, A., Nagler, A., Granulocyte-colony stimulating factor for hematopoietic stem cell donation from healthy female donors during pregnancy and lactation: what do we know? Hum. Reprod. Update. 2013, 19, 259-267.
54. James, E. A., Wang, C., Wang, Z., Reeves, R. et al., Production and Characterization of Biologically Active Human GM-CSF Secreted by Genetically Modified Plant Cells. Protein Expr. Purif. 2000, 19, 131-138.
55. Lee, J.-H., Kim, N.-S., Kwon, T.-H., Jang, Y.-S., Yang, M.-S., Increased production of human granulocyte-macrophage colony stimulating factor (hGM-CSF) by the addition of stabilizing polymer in plant suspension cultures. J. Biotechnol. 2002, 96, 205-211.
56. Kim, N.-S., Kim, T.-G., Jang, Y.-S., Shin, Y. J. et al., Amylase gene silencing by RNA interference improves recombinant hGM-CSF production in rice suspension culture. Plant Mol. Biol. 2008, 68, 369-377.
57. Shin, Y.-J., Hong, S.-Y., Kwon, T.-H., Jang, Y.-S., Yang, M.-S., High level of expression of recombinant human granulocyte-macrophage colony stimulating factor in transgenic rice cell suspension culture. Biotechnol. Bioeng. 2003, 82, 778-783.
58. Kim, T.-G., Lee, H.-J., Jang, Y.-S., Shin, Y.-J. et al., Co-expression of proteinase inhibitor enhances recombinant human granulocyte-macrophage colony stimulating factor production in transgenic rice cell suspension culture. Protein Expr. Purif. 2008, 61, 117-121.
59. Wang, M.-L., Goldstein, C., Su, W., Moore, P., Albert, H., Production of biologically active GM-CSF in sugarcane: a secure biofactory. Transgenic. Res. 2005, 14, 167-178.
60. Sardana, R., Alli, Z., Dudani, A., Tackaberry, E. et al., Biological Activity of Human Granulocyte-Macrophage Colony Stimulating Factor is Maintained in a Fusion with Seed Glutelin Peptide. Transgenic Res. 2002, 11, 521-531.
61. Sardana, R., Dudani, A., Tackaberry, E., Alli, Z. et al., Biologically active human GM-CSF produced in the seeds of transgenic rice plants. Transgenic Res. 2007, 16, 713-721.
62. Wang, X., Lee, D. A., Wang, Y., Wang, L. et al., Membrane-bound interleukin-21 and CD137 ligand induce functional human natural killer cells from peripheral blood mononuclear cells through STAT-3 activation. Clin. Exp. Immunol. 2013, 172, 104-12.
63. Williams, P., Galipeau, J., GMCSF-Interleukin fusion cytokines induce novel immune effectors that can serve as biopharmaceuticals for treatment of autoimmunity and cancer. J. Intern. Med. 2011, 269, 74-84.
64. Magnuson, N. S., Linzmaier, P. M., Reeves, R., An, G. et al., Secretion of Biologically Active Human Interleukin-2 and Interleukin-4 from Genetically Modified Tobacco Cells in Suspension Culture. Protein Expr. Purif. 1998, 13, 45-52.
65. Patel, J., Zhu, H., Menassa, R., Gyenis, L. et al., Elastin-like polypeptide fusions enhance the accumulation of recombinant proteins in tobacco leaves. Transgenic Res. 2007, 16, 239-249.
66. Park, Y., Cheong, H., Expression and Production of Recombinant Human Interleukin-2 in Potato Plants. Protein Expr Purif. 2002, 25, 160-165.
67. Fujiwara, Y., Aiki, Y., Yang, L., Takaiwa, F. et al., Extraction and purification of human interleukin-10 from transgenic rice seeds. Protein Expr. Purif. 2010, 72, 125-130.
68. Bortesi, L., Rossato, M., Schuster, F., Raven, N. et al., Viral and murine interleukin-10 are correctly processed and retain their biological activity when produced in tobacco. BMC Biotechnol. 2009, 9, 1-13.
69. Gutiérrez-Ortega, A., Ávila-Moreno, F., Saucedo-Arias, L. J., Sánchez-Torres, C., Gómez-Lim, M. Á., Expression of a single-chain human interleukin-12 gene in transgenic tobacco plants and functional studies. Biotechnol. Bioeng. 2004, 85, 734-740.
70. Kwon, T. H., Seo, J. E., Kim, J., Lee, J. H. et al., Expression and secretion of the heterodimeric protein interleukin-12 in plant cell suspension culture. Biotechnol. Bioeng. 2003, 81, 870-875.
71. Gutiérrez-Ortega, A., Sandoval-Montes, C., Olivera-Flores, T. J., Santos-Argumedo, L., Gómez-Lim, M. Â., Expression of Functional Interleukin-12 from Mouse in Transgenic Tomato Plants. Transgenic Res. 2005, 14, 877-885.
72. Wang, D. J., Brandsma, M., Yin, Z., Wang, A. et al., A novel platform for biologically active recombinant human interleukin-13 production. Plant Biotechnol. J. 2008, 6, 504-515.
73. Zhang, B., Yang, Y.-H., Lin, Y.-M., Rao, Q. et al., Expression and production of bioactive human interleukin-18 in transgenic tobacco plants. Biotechnol. Lett. 2003, 25, 1629-1635.
74. Moriguchi, H., Sato, C., Treatment of SARS with human interferons. Lancet 2003, 362, 1159.
75. Heim, M. H., Intracellular signalling and antiviral effects of interferons. Dig. Liver Dis. 2000, 32, 257-263.
76. Twyman, R. M., Schillberg, S. R. F., Transgenic plants in the biopharmaceutical market. Expert Opin. Emerg. Drugs. 2005, 10, 185-218.
77. Forbes, B. E., Molecular mechanisms underlying insulin-like growth factor action: How mutations in the GH: IGF axis lead to short stature. Pediatr. Endocrinol. Rev. 2011, 8, 374-381.
78. Ohya, K., Matsumura, T., Ohashi, K., Onuma, M., Sugimoto, C., Expression of two subtypes of human IFN-alpha in transgenic potato plants. J. Interferon Cytokine Res. 2001, 21, 595-602.
79. Sawahel, W. A., The production of transgenic potato plants expressing human alpha-interferon using lipofectin-mediated transformation. Cell. Mol. Biol. Lett. 2002, 7, 19-29.
80. Xie, T., Qiu, Q., Zhang, W., Ning, T. et al., A biologically active rhIGF-1 fusion accumulated in transgenic rice seeds can reduce blood glucose in diabetic mice via oral delivery. Peptides. 2008, 29, 1862-1870.
81. Chen, T.-L., Lin, Y.-L., Lee, Y.-L., Yang, N.-S., Chan, M.-T., Expression of bioactive human interferon-gamma in transgenic rice cell suspension cultures. Transgenic Res. 2004, 13, 499-510.
82. Luchakivskaya, Y., Kishchenko, O., Gerasymenko, I., Olevinskaya, Z. et al., High-level expression of human interferon alpha-2b in transgenic carrot (Daucus carota L.) plants. Plant Cell Rep. 2011, 30, 407-415.
83. Sharma, A. K., Sharma, M. K., Plants as bioreactors: Recent developments and emerging opportunities. Biotechnol. Adv. 2009, 27, 811-832.
84. Arlen, P. A., Falconer, R., Cherukumilli, S., Cole, A. et al., Field production and functional evaluation of chloroplast-derived interferon-α2b. Plant Biotechnol. J. 2007, 5, 511-525.
85. Daniell, H., Ruiz, G., Denes, B., Sandberg, L., Langridge, W., Optimization of codon composition and regulatory elements for expression of human insulin like growth factor-1 in transgenic chloroplasts and evaluation of structural identity and function. BMC Biotechnol. 2009, 9, 1-16.
86. Scotti, N., Rigano, M. M., Cardi, T., Production of foreign proteins using plastid transformation. Biotechnol. Adv. 2012, 30, 387-397.
87. Mahfouz, M. M., Li, L., TALE nucleases and next generation GM crops. GM Crops. 2011, 2, 99-103.
88. Joung, J. K., Sander, J. D., TALENs: a widely applicable technology for targeted genome editing. Nat. Rev. Mol. Cell Biol. 2013, 14, 49-55.
89. Sanjana, N. E., Cong, L., Zhou, Y., Cunniff, M. M. et al., A transcription activator-like effector toolbox for genome engineering. Nat. Protoc. 2012, 7, 171-192.
90. Ramalingam, S., Kandavelou, K., Rajenderan, R., Chandrasegaran, S., Creating Designed Zinc-Finger Nucleases with Minimal Cytotoxicity. J. Mol. Biol. 2011, 405, 630-641.
91. Lovén, J., Hoke, Heather A., Lin, Charles Y., Lau, A. et al., Selective Inhibition of Tumor Oncogenes by Disruption of Super-Enhancers. Cell 2013, 153, 320-334.
92. Whyte, W. A., Orlando, D. A., Hnisz, D., Abraham, B. J. et al., Master Transcription Factors and Mediator Establish Super-Enhancers at Key Cell Identity Genes. Cell 2013, 153, 307-319.
93. Kwon, T.-H., Kim, Y.-S., Lee, J.-H., Yang, M.-S., Production and secretion of biologically active human granulocyte-macrophage colony stimulating factor in transgenic tomato suspension cultures. Biotechnol. Lett. 2003, 25, 1571-1574.
94. Kim, N.-S., Kim, T.-G., Kim, O.-H., Ko, E.-M. et al., Improvement of recombinant hGM-CSF production by suppression of cysteine proteinase gene expression using RNA interference in a transgenic rice culture. Plant Mol. Biol. 2008, 68, 263-275.
95. Góra-Sochacka, A., Redkiewicz, P., Napiórkowska, B., Gaganidze, D. et al., Recombinant mouse granulocyte-macrophage colony-stimulating factor is glycosylated in transgenic tobacco and maintains its biological activity. J. Interferon Cytokine Res. 2010, 30, 135-142.
96. Ma, S., Huang, Y., Davis, A., Yin, Z. et al., Production of biologically active human interleukin-4 in transgenic tobacco and potato. Plant Biotechnol. J. 2005, 3, 309-318.
97. Patel, J., Zhu, H., Menassa, R., Gyenis, L. et al., Elastin-like polypeptide fusions enhance the accumulation of recombinant proteins in tobacco leaves. Transgenic Res. 2007, 16, 239-249.
98. Menassa, R., Kennette, W., Nguyen, V., Rymerson, R. et al., Subcellular targeting of human interleukin-10 in plants. J. Biotechnol. 2004, 108, 179-183.
99. Farran, I., Río-Manterola, F., Íñiguez, M., Gárate, S. et al., High-density seedling expression system for the production of bioactive human cardiotrophin-1, a potential therapeutic cytokine, in transgenic tobacco chloroplasts. Plant Biotechnol. J. 2008, 6, 516-527.
100. Potula, H. H. S., Kathuria, S., Ghosh, A. K., Maiti, T. K., Dey, S., Transient expression, purification and characterization of bioactive human fibroblast growth factor 8b in tobacco plants. Transgenic Res. 2008, 17, 19-32.
101. Lowther, W., Lorick, K., Lawrence, S., Yeow, W.-S., Expression of biologically active human interferon alpha 2 in Aloe vera. Transgenic Res. 2012, 21, 1349-1357.
102. Morandini, F., Avesani, L., Bortesi, L., Van Droogenbroeck, B. et al., Non-food/feed seeds as biofactories for the high-yield production of recombinant pharmaceuticals. Plant Biotechnol. J. 2011, 9, 911-921.
103. Ning, T., Xie, T., Qiu, Q., Yang, W. et al., Oral administration of recombinant human granulocyte-macrophage colony stimulating factor expressed in rice endosperm can increase leukocytes in mice. Biotechnol. Lett. 2008, 30, 1679-1686.
104. Ohya, K., Itchoda, N., Ohashi, K., Onuma, M. et al., Expression of biologically active human tumor necrosis factor-alpha in transgenic potato plant. J. Interferon Cytokine Res. 2002, 22, 371-378.
105. Fukuzawa, N., Tabayashi, N., Okinaka, Y., Furusawa, R. et al., Production of biologically active Atlantic salmon interferon in transgenic potato and rice plants. J. Biosci. Bioeng. 2010, 110, 201-207.
106. Zhou, F., Wang, M.-L., Albert, H., Moore, P., Zhu, Y., Efficient transient expression of human GM-CSF protein in Nicotiana benthamiana using potato virus X vector. Appl. Microbiol. Biotechnol. 2006, 72, 756-762.
107. Musiychuk, K., Sivalenka, R., Jaje, J., Bi, H. et al., Plant-produced human recombinant erythropoietic growth factors support erythroid differentiation in vitro. Stem Cells Dev. 2013, 22, 2326-40.
108. Song, L., Zhao, D., Wu, Y., Li, Y., Transient expression of chicken alpha interferon gene in lettuce. J. Zhejiang Univ. Sci B. 2008, 9, 351-355.
109. Li, J., Chen, M., Liu, X.-W., Zhang, H.-C. et al., Transient expression of an active human interferon-beta in lettuce. Sci. Hortic. (Amsterdam). 2007, 112, 258-265.
110. Nagels, B., Van Damme, E. J. M., Callewaert, N., Zabeau, L. et al., Biologically active, magnICON®-expressed EPO-Fc from stably transformed Nicotiana benthamiana plants presenting tetra-antennary N-glycan structures. J. Biotechnol. 2012, 160, 242-250.
111. Conley, A. J., Joensuu, J. J., Jevnikar, A. M., Menassa, R., Brandle, J. E., Optimization of elastin-like polypeptide fusions for expression and purification of recombinant proteins in plants. Biotechnol. Bioeng. 2009, 103, 562-573.
112. Conley, A. J., Mohib, K., Jevnikar, A. M., Brandle, J. E., Plant recombinant erythropoietin attenuates inflammatory kidney cell injury. Plant Biotechnol. J. 2009, 7, 183-199.
113. Eichler-Stahlberg, A., Weisheit, W., Ruecker, O., Heitzer, M., Strategies to facilitate transgene expression in Chlamydomonas reinhardtii. Planta. 2009, 229, 873-883.
114. Sperb, F., Werlang, I. R., Margis-Pinheiro, M., Basso, L. et al., Molecular Cloning and Transgenic Expression of a Synthetic Human Erythropoietin Gene in Tobacco. Appl. Biochem. Biotechnol. 2011, 165, 652-665.
115. Castilho, A., Neumann, L., Daskalova, S., Mason, H. S. et al., Engineering of Sialylated Mucin-type O-Glycosylation in Plants. J. Biol. Chem. 2012, 287, 36518-36526.
116. Kittur, F., Hung, C.-Y., Darlington, D., Sane, D., Xie, J., N-Glycosylation engineering of tobacco plants to produce asialoerythropoietin. Plant Cell. Rep. 2012, 31, 1233-1243.