Advertisement

Molecular Farming Using Bioreactor-Based Plant Cell Suspension Cultures for Recombinant Protein Production

  • Ting-Kuo Huang
  • Karen A. McDonald
Chapter

Abstract

The need for biomanufacturing capacity for recombinant protein production to meet the expanding pharmaceutical and industrial market demands has gained increasing importance, leading to the development of new protein expression platforms capable of addressing requirements in terms of protein yield, product quality, and production cost. In the past few decades, molecular farming using plant ­cell-based expression systems (whole plants and in vitro plant cells, organ and tissue cultures) have been investigated as an alternative for the large-scale bioproduction of recombinant proteins. Molecular farming using bioreactor-based plant cell suspension cultures provides attractive features over recombinant microbial fermentation and mammalian cell cultures in terms of intrinsic safety, cost-effective biomanufacturing, and the capability for post-translation modifications. The current research and development, emerging techniques, commercialization and future prospects of mole­cular farming using bioreactor-based plant cell suspension cultures for production of recombinant proteins will be discussed in this chapter.

Keywords

Plant Cell Culture Recombinant Protein Production Membrane Bioreactor High Cell Density Culture Oxygen Mass Transfer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. Amanullah A, Buckland BC, Nienow AW (2004) Mixing in the fermentation and cell culture industries. In: Paul EL, Atiemo-Obeng VA, Kresta SM (eds) Handbook of industrial mixing. John Wiley & Sons, Inc., pp 1071–1170Google Scholar
  2. Angell SM, Baulcombe DC (1997) Consistent gene silencing in transgenic plants expressing a replicating potato virus X RNA. EMBO J 16(12):3675–3684Google Scholar
  3. Atkinson RG, Bieleski LRF, Gleave AP, Janssen BJ, Morris BAM (1998) Post-transcriptional silencing of chalcone synthase in petunia using a geminivirus-based episomal vector. Plant J 15(5):593–604Google Scholar
  4. Benchabane M, Goulet C, Rivard D, Faye L, Gomord V, Michaud D (2008) Preventing unintended proteolysis in plant protein biofactories. Plant Biotechnol J 6(7):633–648Google Scholar
  5. Boivin EB, Lepage É, Matton DP, De Crescenzo G, Jolicoeur M (2010) Transient expression of antibodies in suspension plant cell suspension cultures is enhanced when co-transformed with the tomato bushy stunt virus p19 viral suppressor of gene silencing. Biotechnol Prog 26(6):1534–1543Google Scholar
  6. Castilho A, Strasser R, Stadlmann J, Grass J, Jez J, Gattinger P, Kunert R, Quendler H, Pabst M, Leonard R, Altmann F, Steinkellner H (2010) In planta protein sialylation through overexpression of the respective mammalian pathway. J Biol Chem 285:15923–15930. doi: 10.1074/jbc.M109.088401 Google Scholar
  7. Cho JS, Hong SM, Joo SY, Yoo JS, Kim DI (2007) Cryopreservation of transgenic rice suspension cells producing recombinant hCTLA4Ig. Appl Microbiol Biotechnol 73(6):1470–1476Google Scholar
  8. Corrado G, Karali M (2009) Inducible gene expression systems and plant biotechnology. Biotechnol Adv 27(6):733–743Google Scholar
  9. Cosgrove DJ (1997) Relaxation in a high-stress environment: the molecular bases of extensible cell walls and cell enlargement. Plant Cell 9(7):1031–1041Google Scholar
  10. Curtis WR, Emery AH (1993) Plant-cell suspension-culture rheology. Biotechnol Bioeng 42(4):520–526Google Scholar
  11. Curtis WR, Tuerk AL (2006) Oxygen transport in plant tissue culture systems. Plant Tissue Cult Eng 6:173–186Google Scholar
  12. De Dobbeleer C, Cloutier M, Fouilland M, Legros R, Jolicoeur M (2006) A high-rate perfusion bioreactor for plant cells. Biotechnol Bioeng 95(6):1126–1137Google Scholar
  13. De Muynck B, Navarre C, Boutry M (2010) Production of antibodies in plants: status after twenty years. Plant Biotechnol J 8(5):529–563Google Scholar
  14. del Val IJ, Kontoravdi C, Nagy JM (2010) Towards the implementation of quality by design to the production of therapeutic monoclonal antibodies with desired glycosylation patterns. Biotechnol Prog 26(6):1505–1527Google Scholar
  15. Demain AL, Vaishnav P (2009) Production of recombinant proteins by microbes and higher organisms. Biotechnol Adv 27(3):297–306Google Scholar
  16. Dohi K, Nishikiori M, Tamai A, Ishikawa M, Meshi T, Mori M (2006) Inducible virus-mediated expression of a foreign protein in suspension-cultured plant cells. Arch Virol 151(6):1075–1084Google Scholar
  17. Doran P (1993) Design of reactors for plant cells and organs. Bioprocess Des Control 48:115–168Google Scholar
  18. Doran PM (1999) Design of mixing systems for plant cell suspensions in stirred reactors. Biotechnol Prog 15(3):319–335Google Scholar
  19. Doran PM (2006a) Foreign protein degradation and instability in plants and plant tissue cultures. Trends Biotechnol 24(9):426–432Google Scholar
  20. Doran PM (2006b) Loss of secreted antibody from transgenic plant tissue cultures due to surface adsorption. J Biotechnol 122(1):39–54Google Scholar
  21. Dunlop EH, Namdev PK, Rosenberg MZ (1994) Effect of fluid shear forces on plant-cell suspensions. Chem Eng Sci 49(14):2263–2276Google Scholar
  22. Eibl R, Eibl D (2006) Design and use of the wave bioreactor for plant cell culture. Plant Tissue Cult Eng 6:203–227Google Scholar
  23. Eibl R, Eibl D (2008) Design of bioreactors suitable for plant cell and tissue cultures. Phytochem Rev 7(3):593–598Google Scholar
  24. Eibl R, Eibl D, Eibl R, Werner S, Eibl D (2009a) Bag bioreactor based on wave-induced motion: characteristics and applications. In: Disposable bioreactors, vol 115, Advances in biochemical engineering/biotechnology. Springer, Berlin/Heidelberg, pp 55–87Google Scholar
  25. Eibl R, Werner S, Eibl D (2009b) Disposable bioreactors for plant liquid cultures at Litre-scale. Eng Life Sci 9(3):156–164Google Scholar
  26. Eibl R, Kaiser S, Lombriser R, Eibl D (2010) Disposable bioreactors: the current state-of-the-art and recommended applications in biotechnology. Appl Microbiol Biotechnol 86(1):41–49Google Scholar
  27. Faye L, Boulaflous A, Benchabane M, Gomord W, Michaud D (2005) Protein modifications in the plant secretory pathway: current status and practical implications in molecular pharming. Vaccine 23(15):1770–1778Google Scholar
  28. Franconi R, Demurtas OC, Massa S (2010) Plant-derived vaccines and other therapeutics produced in contained systems. Expert Rev Vaccines 9:877–892. doi: 10.1586/erv.10.91 Google Scholar
  29. Gao J, Lee JM (1992) Effect of oxygen supply on the suspension culture of genetically modified tobacco cells. Biotechnol Prog 8(4):285–290Google Scholar
  30. Gilleta F, Roisin C, Fliniaux MA, Jacquin-Dubreuil A, Barbotin JN, Nava-Saucedo JE (2000) Immobilization of Nicotiana tabacum plant cell suspensions within calcium alginate gel beads for the production of enhanced amounts of scopolin. Enzyme Microb Technol 26(2–4):229–234Google Scholar
  31. Gleba Y, Klimyuk V, Marillonnet S (2007) Viral vectors for the expression of proteins in plants. Curr Opin Biotechnol 18(2):134–141Google Scholar
  32. Gomord V, Faye L (2004) Posttranslational modification of therapeutic proteins in plants. Curr Opin Plant Biol 7(2):171–181Google Scholar
  33. Gomord V, Fitchette A-C, Menu-Bouaouiche L, Saint-Jore-Dupas C, Plasson C, Michaud D, Faye L (2010) Plant-specific glycosylation patterns in the context of therapeutic protein production. Plant Biotechnol J 8(5):564–587Google Scholar
  34. Hacker DL, De Jesus M, Wurm FM (2009) 25 years of recombinant proteins from reactor-grown cells – Where do we go from here? Biotechnol Adv 27(6):1023–1027Google Scholar
  35. Hellwig S, Drossard J, Twyman RM, Fischer R (2004) Plant cell cultures for the production of recombinant proteins. Nat Biotechnol 22(11):1415–1422Google Scholar
  36. Hong SY, Kwon TH, Lee JH, Jang YS, Yang MS (2002) Production of biologically active hG-CSF by transgenic plant cell suspension culture. Enzyme Microb Technol 30(6):763–767Google Scholar
  37. Huang T-K, McDonald KA (2009) Bioreactor engineering for recombinant protein production in plant cell suspension cultures. Biochem Eng J 45(3):168–184Google Scholar
  38. Huang TK, Wang PM, Wu WT (2001) Cultivation of Bacillus thuringiensis in an airlift reactor with wire mesh draft tubes. Biochemical Engineering Journal 7(1):35–39Google Scholar
  39. Huang JM, Sutliff TD, Wu LY, Nandi S, Benge K, Terashima M, Ralston AH, Drohan W, Huang N, Rodriguez RL (2001) Expression and purification of functional human alpha-1-antitrypsin from cultured plant cells. Biotechnol Prog 17(1):126–133Google Scholar
  40. Huang TK, Plesha MA, Falk BW, Dandekar AM, McDonald KA (2009) Bioreactor strategies for improving production yield and functionality of a recombinant human protein in transgenic tobacco cell cultures. Biotechnol Bioeng 102(2):508–520Google Scholar
  41. Huang T-K, Plesha MA, McDonald KA (2010) Semicontinuous bioreactor production of a recombinant human therapeutic protein using a chemically inducible viral amplicon expression system in transgenic plant cell suspension cultures. Biotechnol Bioeng 106(3):408–421Google Scholar
  42. James E, Lee JM (2001) The production of foreign proteins from genetically modified plant cells. Adv Biochem Eng Biotechnol 72:127–156Google Scholar
  43. James E, Mills DR, Lee JM (2002) Increased production and recovery of secreted foreign proteins from plant cell cultures using an affinity chromatography bioreactor. Biochem Eng J 12(3):205–213Google Scholar
  44. Junker BH, Stanik M, Barna C, Salmon P, Buckland BC (1998) Influence of impeller type on mass transfer in fermentation vessels. Bioprocess Eng 19(6):403–413Google Scholar
  45. Kaiser J (2008) Is the drought over for pharming? Science 320(5875):473–475. doi: 10.1126/science.320.5875.473 Google Scholar
  46. Kapila J, DeRycke R, VanMontagu M, Angenon G (1997) An Agrobacterium-mediated transient gene expression system for intact leaves (vol 122, p 101, 1997). Plant Sci 124(2):227–227Google Scholar
  47. Kato A, Kawazoe S, Soh Y (1978) Biomass production of tobacco cells.4. Viscosity of broth of tobacco cells in suspension culture. J Ferment Technol 56(3):224–228Google Scholar
  48. Kieran PM (2001) Bioreactor design for plant cell suspension cultures. In: Tramper J, Cabral JMS, Mota M (eds) Multiphase bioreactor design. Taylor & Francis Ltd, Routledge, pp 391–426Google Scholar
  49. Kieran PM, MacLoughlin PF, Malone DM (1997) Plant cell suspension cultures: some engineering considerations. J Biotechnol 59(1–2):39–52Google Scholar
  50. Kieran P, Malone D, MacLoughlin P (2000) Effects of hydrodynamic and interfacial forces on plant cell suspension systems. Influ Stress Cell Growth Prod Form 67:139–177Google Scholar
  51. Kim NS, Kim TG, Kim OH, Ko EM, Jang YS, Jung ES, Kwon TH, Yang MS (2008) Improvement of recombinant hGM-CSF production by suppression of cysteine proteinase gene expression using RNA interference in a transgenic rice culture. Plant Mol Biol 68(3):263–275Google Scholar
  52. Komarnytsky S, Borisjuk N, Yakoby N, Garvey A, Raskin I (2006) Cosecretion of protease inhibitor stabilizes antibodies produced by plant roots. Plant Physiol 141(4):1185–1193Google Scholar
  53. Komarova TV, Baschieri S, Donini M, Marusic C, Benvenuto E, Dorokhov YL (2010) Transient expression systems for plant-derived biopharmaceuticals. Expert Rev Vaccines 9:859–876Google Scholar
  54. Koprivova A, Stemmer C, Altmann F, Hoffmann A, Kopriva S, Gorr G, Reski R, Decker EL (2004) Targeted knockouts of Physcomitrella lacking plant-specific immunogenic N-glycans. Plant Biotechnol J 2(6):517–523Google Scholar
  55. Kumar S, Fladung M (2001) Controlling transgene integration in plants. Trends Plant Sci 6(4):155–159Google Scholar
  56. Lambe P, Dinant M, Matagne RF (1995) Differential long-term expression and methylation of the hygromycin phosphotransferase (Hph) and beta-glucuronidase (Gus) genes in transgenic pearl-millet (Pennisetum-Glaucum) Callus. Plant Sci 108(1):51–62Google Scholar
  57. Lico C, Chen Q, Santi L (2008) Viral vectors for production of recombinant proteins in plants. J Cell Physiol 216(2):366–377Google Scholar
  58. Lienard D, Dinh OT, van Oort E, Van Overtvelt L, Bonneau C, Wambre E, Bardor M, Cosette P, Didier-Laurent A, de Borne FD, Delon R, van Ree R, Moingeon P, Faye L, Gomord V (2007) Suspension-cultured BY-2 tobacco cells produce and mature immunologically active house dust mite allergens. Plant Biotechnol J 5(1):93–108Google Scholar
  59. Lindbo JA (2007) High-efficiency protein expression in plants from agroinfection-compatible Tobacco mosaic virus expression vectors. BMC Biotechnol 7:52–62Google Scholar
  60. Lucumi A, Posten C (2006) Establishment of long-term perfusion cultures of recombinant moss in a pilot tubular photobioreactor. Process Biochem 41(10):2180–2187Google Scholar
  61. Maccarthy JJ, Ratcliffe D, Street HE (1980) The effect of nutrient medium composition on the growth-cycle of catharanthus-roseus G. Don cells grown in batch culture. J Exp Bot 31(124):1315–1326Google Scholar
  62. McDonald KA, Hong LM, Trombly DM, Xie Q, Jackman AP (2005) Production of human alpha-1-antitrypsin from transgenic rice cell culture in a membrane bioreactor. Biotechnol Prog 21(3):728–734Google Scholar
  63. Micheletti M, Barrett T, Doig SD, Baganz F, Levy MS, Woodley JM, Lye GJ (2006) Fluid mixing in shaken bioreactors: implications for scale-up predictions from microlitre-scale microbial and mammalian cell cultures. Chem Eng Sci 61(9):2939–2949Google Scholar
  64. Mihaliak CA, Fanton MJ, Mcmillen JK (2007) Preparation of vaccine master cell lines using recombinant plant suspension cultures United States Patent 20070107086Google Scholar
  65. Miller TJ, Fanton MJ, Webb SR (2006) Stable immunoprophylactic and therapeutic compositions derived from transgenic plant cells and methods for production United States Patent 20060222664Google Scholar
  66. Murphy DJ (2007) Improving containment strategies in biopharming. Plant Biotechnol J 5(5):555–569Google Scholar
  67. Namdev PK, Dunlop EH (1995) Shear sensitivity of plant-cells in suspensions – present and future. Appl Biochem Biotechnol 54(1–3):109–131Google Scholar
  68. Obembe OO, Popoola JO, Leelavathi S, Reddy SV (2011) Advances in plant molecular farming. Biotechnol Adv 29(2):210–222Google Scholar
  69. Offringa R, de Groot MJ, Haagsman HJ, Does MP, van den Elzen PJ, Hooykaas PJ (1990) Extrachromosomal homologous recombination and gene targeting in plant cells after Agrobacterium mediated transformation. EMBO J 9(10):3077–3084Google Scholar
  70. Osuna L, Moyano E, Mangas S, Bonfill M, Cusido RM, Pinol MT, Zamilpa A, Tortoriello J, Palazon J (2008) Immobilization of Galphimia glauca plant cell suspensions for the production of enhanced amounts of Galphimine-B. Planta Med 74(1):94–99Google Scholar
  71. Padidam M (2003) Chemically regulated gene expression in plants. Curr Opin Plant Biol 6(2):169–177Google Scholar
  72. Plesha MA, Huang TK, Dandekar AM, Falk BW, McDonald KA (2007) High-level transient production of a heterologous protein in plants by optimizing induction of a chemically inducible viral amplicon expression system. Biotechnol Prog 23(6):1277–1285Google Scholar
  73. Plesha MA, Huang TK, Dandekar AM, Falk BW, McDonald KA (2009) Optimization of the bioprocessing conditions for scale-up of transient production of a heterologous protein in plants using a chemically inducible viral amplicon expression system. Biotechnol Prog 25(3):722–734Google Scholar
  74. Pogue GP, Vojdani F, Palmer KE, Hiatt E, Hume S, Phelps J, Long L, Bohorova N, Kim D, Pauly M, Velasco J, Whaley K, Zeitlin L, Garger SJ, White E, Bai Y, Haydon H, Bratcher B (2010) Production of pharmaceutical-grade recombinant aprotinin and a monoclonal antibody product using plant-based transient expression systems. Plant Biotechnol J 8(5):638–654Google Scholar
  75. Qi HN, Goudar CT, Michaels JD, Henzler HJ, Jovanovic GN, Konstantinov KB (2003) Experimental and theoretical analysis of tubular membrane aeration for mammalian cell bioreactors. Biotechnol Prog 19(4):1183–1189Google Scholar
  76. Rao AQ, Bakhsh A, Kiani S, Shahzad K, Shahid AA, Husnain T, Riazuddin S (2009) The myth of plant transformation. Biotechnol Adv 27(6):753–763Google Scholar
  77. Ratner M (2010) Pfizer stakes a claim in plant cell-made biopharmaceuticals. Nat Biotechnol 28(2):107–108Google Scholar
  78. Rawel HM, Kroll J, Kulling S (2007) Effect of non-protein components on the degradability of proteins. Biotechnol Adv 25(6):611–613Google Scholar
  79. Read EK, Park JT, Shah RB, Riley BS, Brorson KA, Rathore AS (2009) Process analytical technology (PAT) for biopharmaceutical products: Part I. concepts and applications. Biotechnol Bioeng 105(2):276–284Google Scholar
  80. Samalova M, Brzobohaty B, Moore I (2005) pOp6/LhGR: a stringently regulated and highly responsive dexamethasone-inducible gene expression system for tobacco. Plant J 41(6):919–935Google Scholar
  81. Schahs M, Strasser R, Stadlmann J, Kunert R, Rademacher T, Steinkellner H (2007) Production of a monoclonal antibody in plants with a humanized N-glycosylation pattern. Plant Biotechnol J 5(5):657–663Google Scholar
  82. Schiermeyer A, Schinkel H, Apel S, Fischer R, Schillberg S (2005) Production of Desmodus rotundas salivary plasminogen activator alpha 1 (DSPA alpha 1) in tobacco is hampered by proteolysis. Biotechnol Bioeng 89(7):848–858Google Scholar
  83. Schmale K, Rademacher T, Fischer R, Hellwig S (2006) Towards industrial usefulness – cryo-cell-banking of transgenic BY-2 cell cultures. J Biotechnol 124(1):302–311Google Scholar
  84. Sethuraman N, Stadheim TA (2006) Challenges in therapeutic glycoprotein production. Curr Opin Biotechnol 17(4):341–346Google Scholar
  85. 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):579–590Google Scholar
  86. Shaaltiel Y, Baum G, Bartfeld D, Hashmueli S, Lewkowicz A (2008) Production of high mannose proteins in plant culture. United States Patent 20080038232Google Scholar
  87. Shadwick FS, Doran PM (2005) Foreign Protein Expression Using Plant Cell Suspension and Hairy Root Cultures. In: Fischer R, Schillberg S (eds) Molecular Farming: Plant-Made Pharmaceuticals and Technical Proteins, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, FRG, pp 13–36. doi: 10.1002/3527603638.ch2Google Scholar
  88. Sharma KK, Bhatnagar-Mathur P, Thorpe TA (2005) Genetic transformation technology: status and problems. Vitro Cell Dev BiolPlant 41(2):102–112Google Scholar
  89. Sharp JM, Doran PM (2001a) Characterization of monoclonal antibody fragments produced by plant cells. Biotechnol Bioeng 73(5):338–346Google Scholar
  90. Sharp JM, Doran PM (2001b) Strategies for enhancing monoclonal antibody accumulation in plant cell and organ cultures. Biotechnol Prog 17(6):979–992Google Scholar
  91. Shih SMH, Doran PM (2009) Foreign protein production using plant cell and organ cultures: advantages and limitations. Biotechnol Adv 27(6):1036–1042Google Scholar
  92. Shin YJ, Hong SY, Kwon TH, Jang YS, Yang MS (2003) High level of expression of recombinant human granulocyte-macrophage colony stimulating factor in transgenic rice cell suspension culture. Biotechnol Bioeng 82(7):778–783Google Scholar
  93. Strasser R, Stadlmann J, Schähs M, Stiegler G, Quendler H, Mach L, Glössl J, Weterings K, Pabst M, Steinkellner H (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(4):392–402Google Scholar
  94. Streatfield SJ (2007) Approaches to achieve high-level heterologous protein production in plants. Plant Biotechnol J 5(1):2–15Google Scholar
  95. Su WW, Arias R (2003) Continuous plant cell perfusion culture: bioreactor characterization and secreted enzyme production. J Biosci Bioeng 95(1):13–20Google Scholar
  96. Sudarshana MR, Plesha MA, Uratsu SL, Falk BW, Dandekar AM, Huang TK, McDonald KA (2006) A chemically inducible cucumber mosaic virus amplicon system for expression of heterologous proteins in plant tissues. Plant Biotechnol J 4(5):551–559Google Scholar
  97. Suehara KI, Takao S, Nakamura K, Uozumi N, Kobayashi T (1996) Optimal expression of GUS gene from methyl jasmonate-inducible promoter in high density culture of transformed tobacco cell line BY-2. J Ferment Bioeng 82(1):51–55Google Scholar
  98. Tanaka H (2000) Technological problems in cultivation of plant cells at high density (Reprinted from Biotechnol Bioeng 23:1203–1218, 1981). Biotechnol Bioeng 67(6):775–790Google Scholar
  99. Tanaka H, Semba H, Jitsufuchi T, Harada H (1988) The effect of physical stress on plant-cells in suspension-cultures. Biotechnol Lett 10(7):485–490Google Scholar
  100. Terashima M, Ejiri Y, Hashikawa N, Yoshida H (2001) Utilization of an alternative carbon source for efficient production of human alpha(1)-Antitrypsin by genetically engineered rice cell culture. Biotechnol Prog 17(3):403–406Google Scholar
  101. Terrier B, Courtois D, Henault N, Cuvier A, Bastin M, Aknin A, Dubreuil J, Petiard V (2007) Two new disposable bioreactors for plant cell culture: the wave and undertow bioreactor and the slug bubble bioreactor. Biotechnol Bioeng 96(5):914–923Google Scholar
  102. Travis J (2008) Is the drought over for pharming? Science 320(5875):473–477Google Scholar
  103. Trexler MM, McDonald KA, Jackman AP (2002) Bioreactor production of human α1-antitrypsin using metabolically regulated plant cell cultures. Biotechnol Prog 18(3):501–508Google Scholar
  104. Trexler MM, McDonald KA, Jackman AP (2005) A cyclical semicontinuous process for production of human alpha(1)-antitrypsin using metabolically induced plant cell suspension cultures. Biotechnol Prog 21(2):321–328Google Scholar
  105. Tsoi BMY, Doran PM (2002) Effect of medium properties and additives on antibody stability and accumulation in suspended plant cell cultures. Biotechnol Appl Biochem 35:171–180Google Scholar
  106. Twyman RM, Stoger E, Schillberg S, Christou P, Fischer R (2003) Molecular farming in plants: host systems and expression technology. Trends Biotechnol 21(12):570–578Google Scholar
  107. Vandermaas HM, Dejong ER, Rueb S, Hensgens LAM, Krens FA (1994) Stable transformation and long-term expression of the Gusa reporter gene in callus lines of perennial ryegrass (Lolium-Perenne L). Plant Mol Biol 24(2):401–405Google Scholar
  108. Varley J, Birch J (1999) Reactor design for large scale suspension animal cell culture. Cytotechnology 29(3):177–205Google Scholar
  109. Vaucheret H, Fagard M (2001) Transcriptional gene silencing in plants: targets, inducers and regulators. Trends Genet 17(1):29–35Google Scholar
  110. Wagner F, Vogelmann H (1977) Cultivation of plant tissue culture in bioreactors and formation of secondary metabolites. In: Barz W, Reinhard E, Zenk MH (eds) Plant tissue culture and its biotechnological application. Springer, Berlin, pp 245–252Google Scholar
  111. Wagner B, Fuchs H, Adhami F, Ma Y, Scheiner O, Breiteneder H (2004) Plant virus expression systems for transient production of recombinant allergens in Nicotiana benthamiana. Methods 32(3):227–234Google Scholar
  112. Wang PM, Huang TK, Cheng HP, Chien YH, Wu WT (2002) A modified airlift reactor with high capabilities of liquid mixing and mass transfer. J Chem Eng Japan 35(4):354–35Google Scholar
  113. Wroblewski T, Tomczak A, Michelmore R (2005) Optimization of Agrobacterium-mediated transient assays of gene expression in lettuce, tomato and Arabidopsis. Plant Biotechnol J 3(2):259–273Google Scholar
  114. Zhang XR, Mason H (2006) Bean Yellow Dwarf Virus replicons for high-level transgene expression in transgenic plants and cell cultures. Biotechnol Bioeng 93(2):271–279Google Scholar
  115. Zuo JR, Chua NH (2000) Chemical-inducible systems for regulated expression of plant genes. Curr Opin Biotechnol 11(2):146–151Google Scholar
  116. Zuo JR, Niu QW, Chua NH (2000) An estrogen receptor-based transactivator XVE mediates highly inducible gene expression in transgenic plants. Plant J 24(2):265–273Google Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Department of Chemical Engineering and Materials ScienceUniversity of California – DavisDavisUSA

Personalised recommendations