1932

Abstract

Plant molecular pharming has emerged as a niche technology for the manufacture of pharmaceutical products indicated for chronic and infectious diseases, particularly for products that do not fit into the current industry-favored model of fermenter-based production campaigns. In this review, we explore the areas where molecular pharming can make the greatest impact, including the production of pharmaceuticals that have novel glycan structures or that cannot be produced efficiently in microbes or mammalian cells because they are insoluble or toxic. We also explore the market dynamics that encourage the use of molecular pharming, particularly for pharmaceuticals that are required in small amounts (such as personalized medicines) or large amounts (on a multi-ton scale, such as blood products and microbicides) and those that are needed in response to emergency situations (pandemics and bioterrorism). The impact of molecular pharming will increase as the platforms become standardized and optimized through adoption of good manufacturing practice (GMP) standards for clinical development, offering a new opportunity to produce inexpensive medicines in regional markets that are typically excluded under current business models.

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2014-04-29
2024-06-21
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Literature Cited

  1. Bakker H, Bardor M, Molthoff JW, Gomord V, Elbers I. 1.  et al. 2001. Galactose-extended glycans of antibodies produced by transgenic plants. Proc. Natl. Acad. Sci. USA 98:2899–904 [Google Scholar]
  2. Bakker H, Rouwendal GJ, Karnoup AS, Florack DE, Stoopen GM. 2.  et al. 2006. An antibody produced in tobacco expressing a hybrid β-1,4-galactosyltransferase is essentially devoid of plant carbohydrate epitopes. Proc. Natl. Acad. Sci. USA 103:7577–82 [Google Scholar]
  3. Bardor M, Loutelier-Bourhis C, Paccalet T, Cosette P, Fitchette AC. 3.  et al. 2003. Monoclonal C5-1 antibody produced in transgenic alfalfa plants exhibits a N-glycosylation that is homogenous and suitable for glyco-engineering into human-compatible structures. Plant Biotechnol. J. 1:451–62 [Google Scholar]
  4. Bendandi M, Gocke CD, Kobrin CB, Benko FA, Sternas LA. 4.  et al. 1999. Complete molecular remissions induced by patient-specific vaccination plus granulocyte-monocyte colony-stimulating factor against lymphoma. Nat. Med. 5:1171–77 [Google Scholar]
  5. Bosch D, Castilho A, Loos A, Schots A, Steinkellner H. 5.  2013. N-glycosylation of plant-produced recombinant proteins. Curr. Pharm. Des. 19:5503–12 [Google Scholar]
  6. Bosch D, Schots A. 6.  2010. Plant glycans: friend or foe in vaccine development?. Expert Rev. Vaccines 9:835–42 [Google Scholar]
  7. Canizares MC, Lomonossoff GP, Nicholson L. 7.  2005. Development of cowpea mosaic virus-based vectors for the production of vaccines in plants. Expert Rev. Vaccines 4:687–97 [Google Scholar]
  8. Cardi T, Lenzi P, Maliga P. 8.  2010. Chloroplasts as expression platforms for plant-produced vaccines. Expert Rev. Vaccines 9:893–911 [Google Scholar]
  9. Castilho A, Gattinger P, Grass J, Jez J, Pabst M. 9.  et al. 2011. N-glycosylation engineering of plants for the biosynthesis of glycoproteins with bisected and branched complex N-glycans. Glycobiology 21:813–23 [Google Scholar]
  10. Castilho A, Neumann L, Daskalova S, Mason HS, Steinkellner H. 10.  et al. 2012. Engineering of sialylated mucin-type O-glycosylation in plants. J. Biol. Chem. 287:36518–26 [Google Scholar]
  11. Castilho A, Neumann L, Gattinger P, Strasser R, Vorauer-Uhl K. 11.  et al. 2013. Generation of biologically active multi-sialylated recombinant human EPOFc in plants. PLoS ONE 8:e54836 [Google Scholar]
  12. Castilho A, Strasser R, Stadlmann J, Grass J, Jez J. 12.  et al. 2010. In planta protein sialylation through overexpression of the respective mammalian pathway. J. Biol. Chem. 285:15923–30 [Google Scholar]
  13. Chargelegue D, Drake PM, Obregon P, Prada A, Fairweather N, Ma JK. 13.  2005. Highly immunogenic and protective recombinant vaccine candidate expressed in transgenic plants. Infect. Immun. 73:5915–22 [Google Scholar]
  14. Chen Z, He Y, Shi B, Yang D. 14.  2013. Human serum albumin from recombinant DNA technology: challenges and strategies. Biochim. Biophys. Acta 1830:5515–25 [Google Scholar]
  15. Chikwamba RK, Scott MP, Mejia LB, Mason HS, Wang K. 15.  2003. Localization of a bacterial protein in starch granules of transgenic maize kernels. Proc. Natl. Acad. Sci. USA 100:11127–32 [Google Scholar]
  16. Conley AJ, Joensuu JJ, Richman A, Menassa R. 16.  2011. Protein body-inducing fusions for high-level production and purification of recombinant proteins in plants. Plant Biotechnol. J. 9:419–33 [Google Scholar]
  17. Corthesy B. 17.  1997. Recombinant secretory IgA for immune intervention against mucosal pathogens. Biochem. Soc. Trans. 25:471–75 [Google Scholar]
  18. Cox KM, Sterling JD, Regan JT, Gasdaska JR, Frantz KK. 18.  et al. 2006. Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor. Nat. Biotechnol. 24:1591–97 [Google Scholar]
  19. Daniell H, Singh ND, Mason H, Streatfield SJ. 19.  2009. Plant-made vaccine antigens and biopharmaceuticals. Trends Plant Sci. 14:669–79 [Google Scholar]
  20. D'Aoust MA, Couture MM, Charland N, Trepanier S, Landry N. 20.  et al. 2010. The production of hemagglutinin-based virus-like particles in plants: a rapid, efficient and safe response to pandemic influenza. Plant Biotechnol. J. 8:607–19 [Google Scholar]
  21. Daskalova SM, Radder JE, Cichacz ZA, Olsen SH, Tsaprailis G. 21.  et al. 2010. Engineering of N. benthamiana L. plants for production of N-acetylgalactosamine-glycosylated proteins—towards development of a plant-based platform for production of protein therapeutics with mucin type O-glycosylation. BMC Biotechnol. 10:62 [Google Scholar]
  22. Durocher Y, Butler M. 22.  2009. Expression systems for therapeutic glycoprotein production. Curr. Opin. Biotechnol. 20:700–7 [Google Scholar]
  23. Elbers IJ, Stoopen GM, Bakker H, Stevens LH, Bardor M. 23.  et al. 2001. Influence of growth conditions and developmental stage on N-glycan heterogeneity of transgenic immunoglobulin G and endogenous proteins in tobacco leaves. Plant Physiol. 126:1314–22 [Google Scholar]
  24. 24. Eur. Med. Eval. Agency (EMEA) Comm. Propr. Med. Prod. (CPMP) 2002. Points to consider on quality aspects of medicinal products containing active substances produced by stable transgene expression in higher plants. Doc. EMEA/CPMP/BWP/764/02, EMEA, London
  25. Fischer R, Schillberg S, Buyel JF, Twyman RM. 25.  2013. Commercial aspects of pharmaceutical protein production in plants. Curr. Pharm. Des. 19:5471–77 [Google Scholar]
  26. Fischer R, Schillberg S, Hellwig S, Twyman RM, Drossard J. 26.  2012. GMP issues for recombinant plant-derived pharmaceutical proteins. Biotechnol. Adv. 30:434–39 [Google Scholar]
  27. 27. Food Drug Admin. (FDA), US Dep. Agric. (USDA) 2002. Guidance for industry: drugs, biologics, and medical devices derived from bioengineered plants for use in humans and animals Draft Guid. Doc., FDA, Rock-ville, MD. http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM055424.pdf [Google Scholar]
  28. Forthal DN, Gach JS, Landucci G, Jez J, Strasser R. 28.  et al. 2010. Fc-glycosylation influences Fcγ receptor binding and cell-mediated anti-HIV activity of monoclonal antibody 2G12. J. Immunol. 185:6876–82 [Google Scholar]
  29. Fujiyama K, Furukawa A, Katsura A, Misaki R, Omasa T, Seki T. 29.  2007. Production of mouse monoclonal antibody with galactose-extended sugar chain by suspension cultured tobacco BY2 cells expressing human β(1,4)-galactosyltransferase. Biochem. Biophys. Res. Commun. 358:85–91 [Google Scholar]
  30. Gasdaska JR, Sherwood S, Regan JT, Dickey LF. 30.  2012. An afucosylated anti-CD20 monoclonal antibody with greater antibody-dependent cellular cytotoxicity and B-cell depletion and lower complement-dependent cytotoxicity than rituximab. Mol. Immunol. 50:134–41 [Google Scholar]
  31. Gleba Y, Klimyuk V, Marillonnet S. 31.  2005. Magnifection—a new platform for expressing recombinant vaccines in plants. Vaccine 23:2042–48 [Google Scholar]
  32. Gleba Y, Klimyuk V, Marillonnet S. 32.  2007. Viral vectors for the expression of proteins in plants. Curr. Opin. Biotechnol. 18:134–41 [Google Scholar]
  33. Gomord V, Fitchette AC, Menu-Bouaouiche L, Saint-Jore-Dupas C, Plasson C. 33.  et al. 2010. Plant-specific glycosylation patterns in the context of therapeutic protein production. Plant Biotechnol. J. 8:564–87 [Google Scholar]
  34. Haddley K. 34.  2012. Taliglucerase alfa for the treatment of Gaucher's disease. Drugs Today 48:525–32 [Google Scholar]
  35. Hastings GE, Wolf PG. 35.  1992. The therapeutic use of albumin. Arch. Fam. Med. 1:281–87 [Google Scholar]
  36. He X, Haselhorst T, von Itzstein M, Kolarich D, Packer NH. 36.  et al. 2012. Production of α-l-iduronidase in maize for the potential treatment of a human lysosomal storage disease. Nat. Commun. 3:1062 [Google Scholar]
  37. He Y, Ning T, Xie T, Qiu Q, Zhang L. 37.  et al. 2011. Large-scale production of functional human serum albumin from transgenic rice seeds. Proc. Natl. Acad. Sci. USA 108:19078–83 [Google Scholar]
  38. Hefferon K. 38.  2013. Plant-derived pharmaceuticals for the developing world. Biotechnol. J. 8:1193–202 [Google Scholar]
  39. Hellwig S, Drossard J, Twyman RM, Fischer R. 39.  2004. Plant cell cultures for the production of recombinant proteins. Nat. Biotechnol. 22:1415–22 [Google Scholar]
  40. Hofbauer A, Stoger E. 40.  2013. Subcellular accumulation and modification of pharmaceutical proteins in different plant tissues. Curr. Pharm. Des. 19:5495–502 [Google Scholar]
  41. Hood EE, Devaiah SP, Fake G, Egelkrout E, Teoh KT. 41.  et al. 2012. Manipulating corn germplasm to increase recombinant protein accumulation. Plant Biotechnol. J. 10:20–30 [Google Scholar]
  42. Hood EE, Kusnadi A, Nikolov Z, Howard JA. 42.  1999. Molecular farming of industrial proteins from transgenic maize. Adv. Exp. Med. Biol. 464:127–47 [Google Scholar]
  43. Hsu FJ, Caspar CB, Czerwinski D, Kwak LW, Liles TM. 43.  et al. 1997. Tumor-specific idiotype vaccines in the treatment of patients with B-cell lymphoma—long-term results of a clinical trial. Blood 89:3129–35 [Google Scholar]
  44. Jacob SS, Cherian S, Sumithra TG, Raina OK, Sankar M. 44.  2013. Edible vaccines against veterinary parasitic diseases—current status and future prospects. Vaccine 31:1879–85 [Google Scholar]
  45. Karnoup AS, Turkelson V, Anderson WH. 45.  2005. O-linked glycosylation in maize-expressed human IgA1. Glycobiology 15:965–81 [Google Scholar]
  46. Kirchhoff J, Raven N, Boes A, Roberts JL, Russell S. 46.  et al. 2012. Monoclonal tobacco cell lines with enhanced recombinant protein yields can be generated from heterogeneous cell suspension cultures by flow sorting. Plant Biotechnol. J. 10:936–44 [Google Scholar]
  47. Klimyuk V, Pogue G, Herz S, Butler J, Haydon H. 47.  2014. Production of recombinant antigens and antibodies in Nicotiana benthamiana using “magnifection” technology: GMP-compliant facilities for small- and large-scale manufacturing. Curr. Top. Microbiol. Immunol 375:127–54 [Google Scholar]
  48. Ko K, Tekoah Y, Rudd PM, Harvey DJ, Dwek RA. 48.  et al. 2003. Function and glycosylation of plant-derived antiviral monoclonal antibody. Proc. Natl. Acad. Sci. USA 100:8013–18 [Google Scholar]
  49. Kogelberg H, Tolner B, Sharma SK, Lowdell MW, Qureshi U. 49.  et al. 2007. Clearance mechanism of a mannosylated antibody-enzyme fusion protein used in experimental cancer therapy. Glycobiology 17:36–45 [Google Scholar]
  50. Kohli N, Westerveld DR, Ayache AC, Verma A, Shil P. 50.  et al. 2014. Oral delivery of bioencapsulated proteins across blood-brain and blood-retinal barriers. Mol. Ther. 22535–46 [Google Scholar]
  51. Komori R, Amano Y, Ogawa-Ohnishi M, Matsubayashi Y. 51.  2009. Identification of tyrosylprotein sulfotransferase in Arabidopsis. Proc. Natl. Acad. Sci. USA 106:15067–72 [Google Scholar]
  52. Koprivova A, Stemmer C, Altmann F, Hoffmann A, Kopriva S. 52.  et al. 2004. Targeted knockouts of Physcomitrella lacking plant-specific immunogenic N-glycans. Plant Biotechnol. J. 2:517–23 [Google Scholar]
  53. Lakshmi PS, Verma D, Yang X, Lloyd B, Daniell H. 53.  2013. Low cost tuberculosis vaccine antigens in capsules: expression in chloroplasts, bio-encapsulation, stability and functional evaluation in vitro. PLoS ONE 8:e54708 [Google Scholar]
  54. Lico C, Chen Q, Santi L. 54.  2008. Viral vectors for production of recombinant proteins in plants. J. Cell. Physiol. 216:366–77 [Google Scholar]
  55. Llop-Tous I, Ortiz M, Torrent M, Ludevid MD. 55.  2011. The expression of a xylanase targeted to ER-protein bodies provides a simple strategy to produce active insoluble enzyme polymers in tobacco plants. PLoS ONE 6:e19474 [Google Scholar]
  56. Ma JK, Barros E, Bock R, Christou P, Dale PJ. 56.  et al. 2005. Molecular farming for new drugs and vaccines. Current perspectives on the production of pharmaceuticals in transgenic plants. EMBO Rep. 6:593–99 [Google Scholar]
  57. Ma JK, Drake PM, Christou P. 57.  2003. The production of recombinant pharmaceutical proteins in plants. Nat. Rev. Genet. 4:794–805 [Google Scholar]
  58. Ma JK, Hiatt A, Hein M, Vine ND, Wang F. 58.  et al. 1995. Generation and assembly of secretory antibodies in plants. Science 268:716–19 [Google Scholar]
  59. Maliga P, Bock R. 59.  2011. Plastid biotechnology: food, fuel, and medicine for the 21st century. Plant Physiol 155:1501–10 [Google Scholar]
  60. Marillonnet S, Thoeringer C, Kandzia R, Klimyuk V, Gleba Y. 60.  2005. Systemic Agrobacterium tumefaciens–mediated transfection of viral replicons for efficient transient expression in plants. Nat. Biotechnol. 23:718–23 [Google Scholar]
  61. Martoglio B, Dobberstein B. 61.  1998. Signal sequences: more than just greasy peptides. Trends Cell Biol. 8:410–15 [Google Scholar]
  62. Masip G, Sabalza M, Perez-Massot E, Banakar R, Cebrian D. 62.  et al. 2013. Paradoxical EU agricultural policies on genetically engineered crops. Trends Plant Sci. 18:312–24 [Google Scholar]
  63. Matsubayashi Y. 63.  2011. Post-translational modifications in secreted peptide hormones in plants. Plant Cell Physiol. 52:5–13 [Google Scholar]
  64. Matsuo K, Matsumura T. 64.  2011. Deletion of fucose residues in plant N-glycans by repression of the GDP-mannose 4,6-dehydratase gene using virus-induced gene silencing and RNA interference. Plant Biotechnol. J. 9:264–81 [Google Scholar]
  65. McCormick AA. 65.  2011. Tobacco derived cancer vaccines for non-Hodgkin's lymphoma: perspectives and progress. Hum. Vaccines 7:305–12 [Google Scholar]
  66. Nagels B, Van Damme EJ, Pabst M, Callewaert N, Weterings K. 66.  2011. Production of complex multiantennary N-glycans in Nicotiana benthamiana plants. Plant Physiol. 155:1103–12 [Google Scholar]
  67. Nandi S, Yalda D, Lu S, Nikolov Z, Misaki R. 67.  et al. 2005. Process development and economic evaluation of recombinant human lactoferrin expressed in rice grain. Transgenic Res. 14:237–49 [Google Scholar]
  68. Nausch H, Mikschofsky H, Koslowski R, Meyer U, Broer I, Huckauf J. 68.  2012. High-level transient expression of ER-targeted human interleukin 6 in Nicotiana benthamiana. PLoS ONE 7:e48938 [Google Scholar]
  69. Neuhaus JM, Rogers JC. 69.  1998. Sorting of proteins to vacuoles in plant cells. Plant Mol. Biol. 38:127–44 [Google Scholar]
  70. Nuttall J, Vine N, Hadlington JL, Drake P, Frigerio L, Ma JK. 70.  2002. ER-resident chaperone interactions with recombinant antibodies in transgenic plants. Eur. J. Biochem. 269:6042–51 [Google Scholar]
  71. Nykiforuk CL, Boothe JG. 71.  2012. Transgenic expression of therapeutic proteins in Arabidopsis thaliana seed. Methods Mol. Biol. 899:239–64 [Google Scholar]
  72. Nykiforuk CL, Boothe JG, Murray EW, Keon RG, Goren HJ. 72.  et al. 2006. Transgenic expression and recovery of biologically active recombinant human insulin from Arabidopsis thaliana seeds. Plant Biotechnol. J. 4:77–85 [Google Scholar]
  73. Nykiforuk CL, Shen Y, Murray EW, Boothe JG, Busseuil D. 73.  et al. 2011. Expression and recovery of biologically active recombinant Apolipoprotein AIMilano from transgenic safflower (Carthamus tinctorius) seeds. Plant Biotechnol. J. 9:250–63 [Google Scholar]
  74. Oey M, Lohse M, Kreikemeyer B, Bock R. 74.  2009. Exhaustion of the chloroplast protein synthesis capacity by massive expression of a highly stable protein antibiotic. Plant J. 57:436–45 [Google Scholar]
  75. Orita T, Oh-eda M, Hasegawa M, Kuboniwa H, Esaki K, Ochi N. 75.  1994. Polypeptide and carbohydrate structure of recombinant human interleukin-6 produced in Chinese hamster ovary cells. J. Biochem. 115:345–50 [Google Scholar]
  76. Palacpac NQ, Yoshida S, Sakai H, Kimura Y, Fujiyama K. 76.  et al. 1999. Stable expression of human β1,4-galactosyltransferase in plant cells modifies N-linked glycosylation patterns. Proc. Natl. Acad. Sci. USA 96:4692–97 [Google Scholar]
  77. Parmenter DL, Boothe JG, van Rooijen GJ, Yeung EC, Moloney MM. 77.  1995. Production of biologically active hirudin in plant seeds using oleosin partitioning. Plant Mol. Biol. 29:1167–80 [Google Scholar]
  78. Parsons J, Altmann F, Arrenberg CK, Koprivova A, Beike AK. 78.  et al. 2012. Moss-based production of asialo-erythropoietin devoid of Lewis A and other plant-typical carbohydrate determinants. Plant Biotechnol. J. 10:851–61 [Google Scholar]
  79. Paul MJ, Teh AY, Twyman RM, Ma JK. 79.  2013. Target product selection—where can molecular pharming make the difference?. Curr. Pharm. Des. 19:5478–85 [Google Scholar]
  80. Phoolcharoen W, Bhoo SH, Lai H, Ma JK, Arntzen CJ. 80.  et al. 2011. Expression of an immunogenic Ebola immune complex in Nicotiana benthamiana. Plant Biotechnol. J. 9:807–16 [Google Scholar]
  81. Pogue GP, Vojdani F, Palmer KE, Hiatt E, Hume S. 81.  et al. 2010. Production of pharmaceutical-grade recombinant aprotinin and a monoclonal antibody product using plant-based transient expression systems. Plant Biotechnol. J. 8:638–54 [Google Scholar]
  82. Rademacher T, Sack M, Arcalis E, Stadlmann J, Balzer S. 82.  et al. 2008. Recombinant antibody 2G12 produced in maize endosperm efficiently neutralizes HIV-1 and contains predominantly single-GlcNAc N-glycans. Plant Biotechnol. J. 6:189–201 [Google Scholar]
  83. Ramessar K, Rademacher T, Sack M, Stadlmann J, Platis D. 83.  et al. 2008. Cost-effective production of a vaginal protein microbicide to prevent HIV transmission. Proc. Natl. Acad. Sci. USA 105:3727–32 [Google Scholar]
  84. Robinson DG, Oliviusson P, Hinz G. 84.  2005. Protein sorting to the storage vacuoles of plants: a critical appraisal. Traffic 6:615–25 [Google Scholar]
  85. Rouwendal GJ, Florack DE, Hesselink T, Cordewener JH, Helsper JP, Bosch D. 85.  2009. Synthesis of Lewis X epitopes on plant N-glycans. Carbohydr. Res. 344:1487–93 [Google Scholar]
  86. Rouwendal GJ, Wuhrer M, Florack DE, Koeleman CA, Deelder AM. 86.  et al. 2007. Efficient introduction of a bisecting GlcNAc residue in tobacco N-glycans by expression of the gene encoding human N-acetylglucosaminyltransferase III. Glycobiology 17:334–44 [Google Scholar]
  87. Sainsbury F, Lavoie PO, D'Aoust MA, Vezina LP, Lomonossoff GP. 87.  2008. Expression of multiple proteins using full-length and deleted versions of cowpea mosaic virus RNA-2. Plant Biotechnol. J. 6:82–92 [Google Scholar]
  88. Sainsbury F, Lomonossoff GP. 88.  2008. Extremely high-level and rapid transient protein production in plants without the use of viral replication. Plant Physiol. 148:1212–18 [Google Scholar]
  89. Saunders K, Lomonossoff GP. 89.  2013. Exploiting plant virus-derived components to achieve in planta expression and for templates for synthetic biology applications. New Phytol. 200:16–26 [Google Scholar]
  90. Schahs M, Strasser R, Stadlmann J, Kunert R, Rademacher T, Steinkellner H. 90.  2007. Production of a monoclonal antibody in plants with a humanized N-glycosylation pattern. Plant Biotechnol. J. 5:657–63 [Google Scholar]
  91. Schillberg S, Raven N, Fischer R, Twyman RM, Schiermeyer A. 91.  2013. Molecular farming of pharmaceutical proteins using plant suspension cell and tissue cultures. Curr. Pharm. Des. 19:5531–42 [Google Scholar]
  92. Schmidt SR. 92.  2013. Protein bodies in nature and biotechnology. Mol. Biotechnol. 54:257–68 [Google Scholar]
  93. Schouten A, Roosien J, van Engelen FA, de Jong GA, Borst-Vrenssen AW. 93.  et al. 1996. The C-terminal KDEL sequence increases the expression level of a single-chain antibody designed to be targeted to both the cytosol and the secretory pathway in transgenic tobacco. Plant Mol. Biol. 30:781–93 [Google Scholar]
  94. Scotti N, Rybicki EP. 94.  2013. Virus-like particles produced in plants as potential vaccines. Expert Rev. Vaccines 12:211–24 [Google Scholar]
  95. Sealover NR, Davis AM, Brooks JK, George HJ, Kayser KJ, Lin N. 95.  2013. Engineering Chinese hamster ovary (CHO) cells for producing recombinant proteins with simple glycoforms by zinc-finger nuclease (ZFN)–mediated gene knockout of mannosyl (alpha-1,3-)-glycoprotein beta-1,2-N-acetylglucosaminyltransferase (Mgat1). J. Biotechnol. 167:24–32 [Google Scholar]
  96. Seifert GJ, Roberts K. 96.  2007. The biology of arabinogalactan proteins. Annu. Rev. Plant Biol. 58:137–61 [Google Scholar]
  97. Shaaltiel Y, Bartfeld D, Hashmueli S, Baum G, Brill-Almon E. 97.  et al. 2007. Production of glucocerebrosidase with terminal mannose glycans for enzyme replacement therapy of Gaucher's disease using a plant cell system. Plant Biotechnol. J. 5:579–90 [Google Scholar]
  98. Shattock RJ, Moore JP. 98.  2003. Inhibiting sexual transmission of HIV-1 infection. Nat. Rev. Microbiol. 1:25–34 [Google Scholar]
  99. Shields RL, Lai J, Keck R, O'Connell LY, Hong K. 99.  et al. 2002. Lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human FcγRIII and antibody-dependent cellular toxicity. J. Biol. Chem. 277:26733–40 [Google Scholar]
  100. Shin YJ, Chong YJ, Yang MS, Kwon TH. 100.  2011. Production of recombinant human granulocyte macrophage-colony stimulating factor in rice cell suspension culture with a human-like N-glycan structure. Plant Biotechnol. J. 9:1109–19 [Google Scholar]
  101. Shoji Y, Chichester JA, Bi H, Musiychuk K, de la Rosa P. 101.  et al. 2008. Plant-expressed HA as a seasonal influenza vaccine candidate. Vaccine 26:2930–34 [Google Scholar]
  102. Showalter AM. 102.  2001. Arabinogalactan-proteins: structure, expression and function. Cell. Mol. Life Sci. 58:1399–417 [Google Scholar]
  103. Sourrouille C, Marquet-Blouin E, D'Aoust MA, Kiefer-Meyer MC, Seveno M. 103.  et al. 2008. Down-regulated expression of plant-specific glycoepitopes in alfalfa. Plant Biotechnol. J. 6:702–21 [Google Scholar]
  104. Sparrow P, Broer I, Hood EE, Eversole K, Hartung F, Schiemann J. 104.  2013. Risk assessment and regulation of molecular farming—a comparison between Europe and US. Curr. Pharm. Des. 19:5513–30 [Google Scholar]
  105. Spok A, Twyman RM, Fischer R, Ma JK, Sparrow PA. 105.  2008. Evolution of a regulatory framework for pharmaceuticals derived from genetically modified plants. Trends Biotechnol. 26:506–17 [Google Scholar]
  106. Sriraman R, Bardor M, Sack M, Vaquero C, Faye L. 106.  et al. 2004. Recombinant anti-hCG antibodies retained in the endoplasmic reticulum of transformed plants lack core-xylose and core-α(1,3)-fucose residues. Plant Biotechnol. J. 2:279–87 [Google Scholar]
  107. Stoger E, Ma JK, Fischer R, Christou P. 107.  2005. Sowing the seeds of success: pharmaceutical proteins from plants. Curr. Opin. Biotechnol. 16:167–73 [Google Scholar]
  108. Strasser R. 108.  2013. Engineering of human-type O-glycosylation in Nicotiana benthamiana plants. Bioengineered 4:191–96 [Google Scholar]
  109. Strasser R, Altmann F, Mach L, Glossl J, Steinkellner H. 109.  2004. Generation of Arabidopsis thaliana plants with complex N-glycans lacking β1,2-linked xylose and core α1,3-linked fucose. FEBS Lett. 561:132–36 [Google Scholar]
  110. Strasser R, Castilho A, Stadlmann J, Kunert R, Quendler H. 110.  et al. 2009. Improved virus neutralization by plant-produced anti-HIV antibodies with a homogeneous β1,4-galactosylated N-glycan profile. J. Biol. Chem. 284:20479–85 [Google Scholar]
  111. Strasser R, Stadlmann J, Schahs M, Stiegler G, Quendler H. 111.  et al. 2008. Generation of glyco-engineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N-glycan structure. Plant Biotechnol. J. 6:392–402 [Google Scholar]
  112. Suzuki K, Yang L, Takaiwa F. 112.  2012. Transgenic rice accumulating modified cedar pollen allergen Cry j 2 derivatives. J. Biosci. Bioeng. 113:249–51 [Google Scholar]
  113. Takagi H, Hiroi T, Hirose S, Yang L, Takaiwa F. 113.  2010. Rice seed ER-derived protein body as an efficient delivery vehicle for oral tolerogenic peptides. Peptides 31:1421–25 [Google Scholar]
  114. Takaiwa F. 114.  2011. Seed-based oral vaccines as allergen-specific immunotherapies. Hum. Vaccines 7:357–66 [Google Scholar]
  115. Takaiwa F. 115.  2013. Update on the use of transgenic rice seeds in oral immunotherapy. Immunotherapy 5:301–12 [Google Scholar]
  116. Thuenemann EC, Lenzi P, Love AJ, Taliansky M, Becares M. 116.  et al. 2013. The use of transient expression systems for the rapid production of virus-like particles in plants. Curr. Pharm. Des. 19:5564–73 [Google Scholar]
  117. Tregoning JS, Nixon P, Kuroda H, Svab Z, Clare S. 117.  et al. 2003. Expression of tetanus toxin Fragment C in tobacco chloroplasts. Nucleic Acids Res. 31:1174–79 [Google Scholar]
  118. Triguero A, Cabrera G, Cremata JA, Yuen CT, Wheeler J, Ramirez NI. 118.  2005. Plant-derived mouse IgG monoclonal antibody fused to KDEL endoplasmic reticulum-retention signal is N-glycosylated homogeneously throughout the plant with mostly high-mannose-type N-glycans. Plant Biotechnol. J. 3:449–57 [Google Scholar]
  119. Twyman RM, Schillberg S, Fischer R. 119.  2013. Optimizing the yield of recombinant pharmaceutical proteins in plants. Curr. Pharm. Des. 19:5486–94 [Google Scholar]
  120. Twyman RM, Stoger E, Schillberg S, Christou P, Fischer R. 120.  2003. Molecular farming in plants: host systems and expression technology. Trends Biotechnol. 21:570–78 [Google Scholar]
  121. van Rooijen GJ, Moloney MM. 121.  1995. Plant seed oil-bodies as carriers for foreign proteins. Biotechnology 13:72–77 [Google Scholar]
  122. Vasilev N, Grömping U, Lipperts A, Raven N, Fischer R, Schillberg S. 122.  2013. Optimization of BY-2 cell suspension culture medium for the production of a human antibody using a combination of fractional factorial designs and the response surface method. Plant Biotechnol. J. 11:867–74 [Google Scholar]
  123. Verch T, Yusibov V, Koprowski H. 123.  1998. Expression and assembly of a full-length monoclonal antibody in plants using a plant virus vector. J. Immunol. Methods 220:69–75 [Google Scholar]
  124. Vezina LP, Faye L, Lerouge P, D'Aoust MA, Marquet-Blouin E. 124.  et al. 2009. Transient co-expression for fast and high-yield production of antibodies with human-like N-glycans in plants. Plant Biotechnol. J. 7:442–55 [Google Scholar]
  125. Virdi V, Coddens A, De Buck S, Millet S, Goddeeris BM. 125.  et al. 2013. Orally fed seeds producing designer IgAs protect weaned piglets against enterotoxigenic Escherichia coli infection. Proc. Natl. Acad. Sci. USA 110:11809–14 [Google Scholar]
  126. Walsh G, Jefferis R. 126.  2006. Post-translational modifications in the context of therapeutic proteins. Nat. Biotechnol. 24:1241–52 [Google Scholar]
  127. Wen AM, Shukla S, Saxena P, Aljabali AA, Yildiz I. 127.  et al. 2012. Interior engineering of a viral nanoparticle and its tumor homing properties. Biomacromolecules 13:3990–4001 [Google Scholar]
  128. Whaley KJ, Hiatt A, Zeitlin L. 128.  2011. Emerging antibody products and Nicotiana manufacturing. Hum. Vaccines 7:349–56 [Google Scholar]
  129. Xu J, Okada S, Tan L, Goodrum KJ, Kopchick JJ, Kieliszewski MJ. 129.  2010. Human growth hormone expressed in tobacco cells as an arabinogalactan-protein fusion glycoprotein has a prolonged serum life. Transgenic Res. 19:849–67 [Google Scholar]
  130. Xu J, Tan L, Goodrum KJ, Kieliszewski MJ. 130.  2007. High-yields and extended serum half-life of human interferon α2b expressed in tobacco cells as arabinogalactan-protein fusions. Biotechnol. Bioeng. 97:997–1008 [Google Scholar]
  131. Yang Z, Bennett EP, Jorgensen B, Drew DP, Arigi E. 131.  et al. 2012. Toward stable genetic engineering of human O-glycosylation in plants. Plant Physiol. 160:450–63 [Google Scholar]
  132. Yang Z, Drew DP, Jorgensen B, Mandel U, Bach SS. 132.  et al. 2012. Engineering mammalian mucin-type O-glycosylation in plants. J. Biol. Chem. 287:11911–23 [Google Scholar]
  133. Yusibov V, Rabindran S. 133.  2008. Recent progress in the development of plant derived vaccines. Expert Rev. Vaccines 7:1173–83 [Google Scholar]
  134. Yusibov V, Rabindran S, Commandeur U, Twyman RM, Fischer R. 134.  2006. The potential of plant virus vectors for vaccine production. Drugs R & D 7:203–17 [Google Scholar]
  135. Yusibov V, Streatfield SJ, Kushnir N, Roy G, Padmanaban A. 135.  2013. Hybrid viral vectors for vaccine and antibody production in plants. Curr. Pharm. Des. 19:5574–86 [Google Scholar]
  136. Zhang P, Chan KF, Haryadi R, Bardor M, Song Z. 136.  2013. CHO glycosylation mutants as potential host cells to produce therapeutic proteins with enhanced efficacy. Adv. Biochem. Eng. Biotechnol. 131:63–87 [Google Scholar]
  137. Zimmermann J, Saalbach I, Jahn D, Giersberg M, Haehnel S. 137.  et al. 2009. Antibody expressing pea seeds as fodder for prevention of gastrointestinal parasitic infections in chickens. BMC Biotechnol. 9:79 [Google Scholar]
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