Skip to main content
SpringerLink
Log in
SpringerLink
Log in

Transgenesis and Plant Molecular Pharming

  • Living reference work entry
  • Latest version View entry history
  • First Online:
Transgenesis and Secondary Metabolism

Part of the book series: Reference Series in Phytochemistry ((RSP))

Abstract

The use of plants as efficient biopharmaceutical factories has significantly increased in the past two decades. This is mainly due to advancements in plant biotechnology which pave the way to high-yield production of biopharmaceuticals in plants, combined with efforts made to optimize yield through upstream, downstream, and preservation strategies of recombinant proteins. The FDA’s approval to commercially release recombinant glucocerebrosidase enzyme produced in carrot cells by Protalix Biotherapeutics was the first plant-produced biopharmaceutical to be released for human consumption into the market. This is a major achievement in the field of molecular pharming. Although many other biopharmaceuticals produced in plants are in the pipeline for commercial release after undergoing various stages of clinical trials, there is room for improvement in enhancing recombinant protein yield in plants. These include exploration of innovative strategies involving genetics, genomics, epigenetics, in silico simulations and purification techniques. In this chapter, we discuss various approaches of plant biotechnology and plant genetic engineering that are being used in the molecular pharming of biopharmaceuticals.

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

Access this chapter

Log in via an institution

Institutional subscriptions

Abbreviations

ADA:

Adenosine deaminase

AGPs:

Arabinogalactan proteins

BY-2:

Bright yellow-2

CaMV:

Cauliflower mosaic virus

CPMV:

Cowpea mosaic virus

DNA:

Deoxyribonucleic acid

ER:

Endoplasmic reticulum

ERT:

Enzyme replacement therapy

FDA:

Food and drug administration

GBP-Fc:

Anti-green fluorescent protein antibody

GMOs:

Genetically modified organisms

HAC1:

Hemagglutinin antigen

HDEL:

H-Histidine D-Aspartic acid, E-Glutamic acid, L-Leucine

hGM-CSF:

Human Granulocyte-macrophage colony-stimulating factor

HIV:

Human immunodeficiency virus

KDEL:

K-Lysine D-Aspartic acid, E-Glutamic acid, L-Leucine

MERS:

Middle East respiratory syndrome

mRNA:

Messenger RNA

Pphas:

β-phaseolin promoter

PpsbA:

Photosystem II protein D1promoter

PSAD:

Photosystem I subunit D1promoter

PVP:

Polyvinylpyrrolidone

PVX:

Potato Virus X

RAmy3D:

Rice α-amylase 3D

RNA:

Ribonucleic acid

SCID:

Severe combined immune deficiency disorders

TMV:

Tobacco mosaic virus

USDA:

United States Department of Agriculture

UTRs:

Untranslated regions

VHH-Fc:

Nanobodies-crystallisable fragments

VLP:

Virus-like particle

VNPs:

Virus-based nanoparticles

References

  1. Winslow L, Kroll DJ (1998) Herbs as medicines. Arch Intern Med 158(20):2192–2199

    Article  CAS  Google Scholar 

  2. Fischer R, Emans N (2000) Molecular farming of pharmaceutical proteins. Transgenic Res 9:279–299

    Article  CAS  Google Scholar 

  3. Fraley RT, Rogers SG, Horsch RB, Sanders PR, Flick JS, Adams SP et al (1983) Expression of bacterial genes in plant cells. Proc Natl Acad Sci 80:4803–4807

    Article  CAS  Google Scholar 

  4. Barta A, Sommergruber K, Thompson D, Hartmuth K, Matzke MA, Matzke AJM (1986) The expression of a nopaline synthase-human growth hormone chimaeric gene in transformed tobacco and sunflower callus tissue. Plant Mol Biol 6:347–357

    Article  CAS  Google Scholar 

  5. De Zoeten GA, Penswick JR, Horisberger MA, Ahl P, Schultze M, Hohn T (1989) The expression, localization, and effect of a human interferon in plants. Virology 172:213–222

    Article  Google Scholar 

  6. Hiatt A, Cafferkey R, Bowdish K (1989) The production of antibodies in transgenic plants. Nature 342:76–78

    Article  CAS  Google Scholar 

  7. Sijmons PC, Dekker BMM, Schrammeijer B, Verwoerd TC, van den Elzen PJM, Hoekema A (1990) Production of correctly processed human serum albumin in transgenic plants. Nat Biotechnol 8(3):217–221

    Article  CAS  Google Scholar 

  8. Makhzoum A, Benyammi R, Moustafa K, Trémouillaux-Guiller J (2014) Recent advances on host plants and expression cassettes’ structure and function in plant molecular pharming. BioDrugs 28:145–159

    Article  CAS  Google Scholar 

  9. Soria-Guerra RE, Moreno-Fierros L, Rosales-Mendoza S (2011) Two decades of plant-based candidate vaccines: a review of the chimeric protein approaches. Plant Cell Rep 30:1367–1382

    Article  CAS  Google Scholar 

  10. Kaiser J (2008) Is the drought over for pharming? Science 320:473–475

    Article  CAS  Google Scholar 

  11. Pfizer Press Releases (2012) Pfizer and Protalix BioTherapeutics Announce FDA Approval Of Elelyso™ (taliglucerase alfa) For The Treatment Of Gaucher Disease. http://press.pfizer.com/press-release/pfizer-and-protalix-biotherapeutics-announce-fda-approval-elelyso-taliglucerase-alfa-t. Accessed 04th July 2016

  12. Singhabahu S, George J, Bringloe DH (2015) High yield production of apoplast-directed human adenosine deaminase in transgenic tobacco BY-2 cell suspensions. Biotechnol Appl Biochem 62(1):87–93

    Article  CAS  Google Scholar 

  13. Makhzoum AB, Sharma P, Bernards MA, Trémouillaux-Guiller J (2013) Hairy roots: an ideal platform for transgenic plant production and other promising applications. In: Gang RD (ed) Phytochemicals, plant growth, and the environment. Springer, New York, pp 95–142

    Chapter  Google Scholar 

  14. Oey M, Lohse M, Kreikemeyer B, Bock R (2009) Exhaustion of the chloroplast protein synthesis capacity by massive expression of a highly stable protein antibiotic. Plant J 57:436–445

    Article  CAS  Google Scholar 

  15. Boyhan D, Daniell H (2011) Low-cost production of proinsulin in tobacco and lettuce chloroplasts for injectable or oral delivery of functional insulin and C-peptide. Plant Biotechnol J 9(5):585–598

    Article  CAS  Google Scholar 

  16. Singhabahu S, George J, Bringloe DH (2013) Expression of functional human adenosine deaminase in tobacco plants. Transgenic Res 22(3):643–649

    Article  CAS  Google Scholar 

  17. Skarjinskaia M, Ruby K, Araujo A, Taylor K, Gopalasamy-Raju V, Musiychuk K et al (2013) Hairy roots as a vaccine production and delivery system. In: Doran MP (ed) Biotechnology of hairy root systems. Springer, Berlin/Heidelberg, pp 115–134

    Chapter  Google Scholar 

  18. Moustafa K, Makhzoum A, Trémouillaux-Guiller J (2016) Molecular farming on rescue of pharma industry for next generations. Crit Rev Biotechnol 36(5):840–850

    CAS  Google Scholar 

  19. Sasou A, Shigemitsu T, Saito Y, Tanaka M, Morita S, Masumura T (2016) Control of foreign polypeptide localization in specific layers of protein body type I in rice seed. Plant Cell Rep 35:1287–1295

    Article  CAS  Google Scholar 

  20. Rosales-Mendoza S, Tello-Olea MA (2015) Carrot cells: a pioneering platform for biopharmaceuticals production. Mol Biotechnol 57(3):219–232

    Article  CAS  Google Scholar 

  21. Merlin M, Gecchele E, Arcalis E, Remelli S, Brozzetti A, Pezzotti M, Avesani L (2016) Enhanced GAD65 production in plants using the MagnICON transient expression system: optimization of upstream production and downstream processing. Biotechnol J 11:542–553

    Article  CAS  Google Scholar 

  22. Barahimipour R, Neupert J, Bock R (2016) Efficient expression of nuclear transgenes in the green alga Chlamydomonas: synthesis of an HIV antigen and development of a new selectable marker. Plant Mol Biol 90(4):403–418

    Article  CAS  Google Scholar 

  23. Vamvaka E, Twyman RM, Murad AM, Melnik S, Teh AY-H, Arcalis E et al (2016) Rice endosperm produces an underglycosylated and potent form of the HIV-neutralizing monoclonal antibody 2G12. Plant Biotechnol J 14:97–108

    Article  CAS  Google Scholar 

  24. Chan H-T, Xiao Y, Weldon WC, Oberste SM, Chumakov K, Daniell H (2016) Cold chain and virus-free chloroplast-made booster vaccine to confer immunity against different poliovirus serotypes. Plant Biotechnol J 11:2190–2200

    Google Scholar 

  25. Hensel G, Floss DM, Arcalis E, Sack M, Melnik S et al (2015) Transgenic production of an anti HIV antibody in the Barley endosperm. PLoS One 10(10), e0140476

    Article  CAS  Google Scholar 

  26. Mbewana S, Mortimer E, Francisco P, Hitzeroth II, Edward R (2015) Production of H5N1 influenza virus matrix protein 2 ectodomain protein bodies in tobacco plants and in insect cells as a candidate universal influenza vaccine. Front Bioeng Biotechnol 3:197

    Article  Google Scholar 

  27. Tinazzi E, Merlin M, Bason C, Beri R, Zampieri R, Lico C et al (2015) Plant-derived chimeric virus particles for the diagnosis of primary Sjögren syndrome. Front Plant Sci 6:1080

    Article  Google Scholar 

  28. Soh HS, Chung HY, Lee HH, Ajjappala H, Jang K, Park J-H et al (2015) Expression and functional validation of heat-labile enterotoxin B (LTB) and cholera toxin B (CTB) subunits in transgenic rice (Oryza sativa). Springer Plus 4(1):1–14

    Article  Google Scholar 

  29. Nahampun HN, Bosworth B, Cunnick J, Mogler M, Wang K (2015) Expression of H3N2 nucleoprotein in maize seeds and immunogenicity in mice. Plant Cell Rep 34(6):969–980

    Article  CAS  Google Scholar 

  30. Mardanova ES, Kotlyarov RY, Kuprianov VV, Stepanova LA, Tsybalova LM, Lomonosoff GP et al (2015) Rapid high-yield expression of a candidate influenza vaccine based on the ectodomain of M2 protein linked to flagellin in plants using viral vectors. BMC Biotechnol 15(1):1–10

    Article  CAS  Google Scholar 

  31. Su J, Zhub L, Shermanb A, Wangb X, Lina S, Kamesha A et al (2015) Low cost industrial production of coagulation factor IX bioencapsulated in lettuce cells for oral tolerance induction in hemophilia B. Biomaterials 70:84–93

    Article  CAS  Google Scholar 

  32. De Myer T, Laukens B, Nolf J, Van Lerberge E, De Rycke R, De Beuckelaer A et al (2015) Comparison of VHH-Fc antibody production in Arabidopsis thaliana, Nicotiana benthamiana and Pichia pastoris. Plant Biotechnol J 13:938–947

    Article  CAS  Google Scholar 

  33. Bundó M, Montesinos L, Izquierdo E, Campo S, Mieulet D, Guiderdoni E et al (2014) Production of cecropin A antimicrobial peptide in rice seed endosperm. BMC Plant Biol 14(1):1–13

    Article  CAS  Google Scholar 

  34. Schillberg S, Fischer R, Emans N (2003) Molecular farming of recombinant antibodies in plants. Cell Mol Life Sci 60:433–445

    Article  CAS  Google Scholar 

  35. Yao J, Weng Y, Dickey A, Wang KY (2015) Plants as factories for human pharmaceuticals: applications and challenges. Int J Mol Sci 16(12):28549–28565

    Article  CAS  Google Scholar 

  36. Yusibov Y, Mett V, Musiychuk K (2012) Influenza vaccines, antigens, composition and methods. United States Patent 20120034253A1

    Google Scholar 

  37. Takaiwa F, Wakasa Y, Takagi H, Hiroi T (2015) Rice seed for delivery of vaccines to gut mucosal immune tissues. Plant Biotechnol J 13:1041–1055

    Article  CAS  Google Scholar 

  38. Mapp Biopharmaceutical Press Releases (2016) LeafBio announces conclusion of ZMapp™ clinical trial; Therapy to treat Ebola shows promise. http://mappbio.com/leafbio-announces-conclusion-of-zmapp-clinical-trial/. Accessed 20th July 2016

  39. Rybicki EP (2009) Plant-produced vaccines: promise and reality. Drug Discov Today 14:16–24. doi:10.1016/j.drudis.2008.10.002

    Article  CAS  Google Scholar 

  40. Cummings J, Guerrero M, Moon J, Waterman P, Nielsen R, Jefferson S et al (2014) Safety and immunogenicity of a plant-produced recombinant monomer hemagglutinin-based influenza vaccine derived from influenza A (H1N1) pdm09 virus: a phase 1 dose-escalation study in healthy adults. Vaccine 32:2251–2259

    Article  CAS  Google Scholar 

  41. Shoji Y, Farrance CE, Bautista J, Bi H, Musiychuk K, Horsey A et al (2012) A plant-based system for rapid production of influenza vaccine antigens. Influenza Other Respi Viruses 6(3):204–210

    Article  CAS  Google Scholar 

  42. Yuki Y, Mejima M, Kurokawa S, Hiroiwa T, Takahashi Y, Tokuhara D et al (2013) Induction of toxin-specific neutralizing immunity by molecularly uniform rice-based oral cholera toxin B subunit vaccine without plant-associated sugar modification. Plant Biotechnol J 11:799–808

    Article  CAS  Google Scholar 

  43. Nochi T, Yuki Y, Katakai Y, Shibata H, Tokuhara D, Mejima M et al (2009) A rice based oral cholera vaccine induces macaque-specific systemic neutralizing antibodies but does not influence pre-existing intestinal immunity. J Immunol 183:6538–6544

    Article  CAS  Google Scholar 

  44. Chichester J, Jones R, Green B, Stow M, Miao F, Moonsammy G et al (2012) Safety and immunogenicity of a plant-produced recombinant hemagglutinin-based influenza vaccine (HAI-05) derived from A/Indonesia/05/2005 (H5N1) influenza virus: a phase 1 randomized, double-blind, placebo controlled, dose-escalation study in healthy adults. Viruses 4:3227–3244

    Article  CAS  Google Scholar 

  45. Bendandi M, Marillonnet S, Kandzia R, Thieme F, Nickstadt A, Herz S et al (2010) Rapid, high-yield production in plants of individualized idiotype vaccines for non-Hodgkin’s lymphoma. Ann Oncol 21(12):2420–2427

    Article  CAS  Google Scholar 

  46. Tacket C, Pasetti M, Edelman R, Howard J, Streatfield S (2004) Immunogenicity of recombinant LT-B delivered orally to humans in transgenic corn. Vaccine 22:4385–4389

    Article  CAS  Google Scholar 

  47. Mason HS, Haq TA, Clements JD, Arntzen CJ (1998) Edible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT): potatoes expressing a synthetic LT-B gene. Vaccine 16(13):1336–1343

    Article  CAS  Google Scholar 

  48. Yusibov V, Hooper D, Spitsin S, Fleysh N, Kean R, Mikheeva T et al (2002) Expression in plants and immunogenicity of plant virus-based experimental rabies vaccine. Vaccine 20:3155–3164

    Article  CAS  Google Scholar 

  49. Modelska A, Dietzschold B, Sleysh N, Fu ZF, Steplewski K, Hooper DC, Hilary K, Yusibov V (1998) Immunization against rabies with plant-derived antigen. Proc Natl Acad Sci 95(5):2481–2485

    Article  CAS  Google Scholar 

  50. Mason HS, Ball JM, Shi JJ, Jiang X, Estes MK, Arntzen CJ (1996) Expression of Norwalk virus capsid protein in transgenic tobacco and potato and its oral immunogenicity in mice. Proc Natl Acad Sci 93(11):5335–5340

    Article  CAS  Google Scholar 

  51. Influenza A virus vaccine H7N9 – Medicago http://adisinsight.springer.com/drugs/800039770

  52. Williams SCP (2012) Drugmaker reaps what it sows with first plant-made biologic. Nat Med 18(1):5–5

    Article  CAS  Google Scholar 

  53. Pogue GP, Vojdani F, Palmer KE, Hiatt E, Hume S, Phelps J et al (2010) Production of pharmaceutical-grade recombinant aprotinin and a monoclonal antibody product using plant-based transient expression systems. Plant Biotechnol J 8(5):638–654

    Article  CAS  Google Scholar 

  54. Streatfield SJ (2006) Mucosal immunization using recombinant plant-based oral vaccines. Methods 38(2):150–157

    Article  CAS  Google Scholar 

  55. Kapusta J, Modelska A, Figlerowicz M, Pniewski T, Letellier M, Lisowa O et al (1999) A plant-derived edible vaccine against hepatitis B virus. J Fed Am Soc Exp Biol 13(13):1796–1799

    CAS  Google Scholar 

  56. Cox KM, Sterling JD, Regan JT, Gasdaska JR, Frantz KK, Peele CG et al (2006) Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor. Nat Biotechnol 24(12):1591–1597

    Article  CAS  Google Scholar 

  57. Tacket C, Mason H, Losonsky G, Estes M, Levine M, Arntzen C (2000) Human immune responses to a novel norwalk virus vaccine delivered in transgenic potatoes. J Infect Dis 182:302–305

    Article  CAS  Google Scholar 

  58. Yusibov V, Modelska A, Steplewski K, Agadjanyan M, Weiner D, Hooper DC, Koprowski H (1997) Antigens produced in plants by infection with chimeric plant viruses immunize against rabies virus and HIV-1. Proc Natl Acad Sci 94(11):5784–5788

    Article  CAS  Google Scholar 

  59. Shaaltiel Y, Bartfeld D, Hashmueli S, Baum G, Brill-Almon E, Galili G 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(5):579–590

    Article  CAS  Google Scholar 

  60. Markley N, Nykiforuk C, Boothe J, Moloney M (2006) Producing proteins using transgenic Oilbody-Oleosin technology. BioPharm Int 19(6):34–37

    CAS  Google Scholar 

  61. Zhong Q, Gu Z, Glatz CE (2006) Extraction of recombinant dog gastric lipase from transgenic corn seed. J Agric Food Chem 54(21):8086–8092

    Article  CAS  Google Scholar 

  62. Samyn-Petit B, Gruber V, Flahaut C, Wajda-Dubos JP, Farrer S, Pons A et al (2001) N-glycosylation potential of maize: the human lactoferrin used as a model. Glycoconj J 18(7):519–527

    Article  CAS  Google Scholar 

  63. Takeyama N, Kiyono H, Yuki Y (2015) Plant-based vaccines for animals and humans: recent advances in technology and clinical trials. Ther Adv Vaccines 3(5–6):139–154

    Article  Google Scholar 

  64. Yusibov V, Streatfield SJ, Kushnir N (2011) Clinical development of plant-produced recombinant pharmaceuticals: vaccines, antibodies and beyond. Hum Vaccin 7(3):313–321

    Article  CAS  Google Scholar 

  65. Paul M, Ma JKC (2011) Plant-made pharmaceuticals: leading products and production platforms. Biotechnol Appl Biochem 58(1):58–67

    Article  CAS  Google Scholar 

  66. Odell JT, Nagy F, Chua NH (1985) Identification of DNA sequences required for activity of the cauliflower mosaic virus 35S promoter. Nature 313:810–812

    Article  CAS  Google Scholar 

  67. Mason HS, Lam DM, Arntzen CJ (1992) Expression of hepatitis B surface antigen in transgenic plants. Proc Natl Acad Sci 89(24):11745–11749

    Article  CAS  Google Scholar 

  68. Panahi M, Alli Z, Cheng X, Belbaraka L, Belgoudi J, Sardana R et al (2004) Recombinant protein expression plasmids optimized for industrial E. coli fermentation and plant systems produce biologically active human insulin-like growth factor-1 in transgenic rice and tobacco plants. Transgenic Res 13(3):245–259

    Article  CAS  Google Scholar 

  69. Torres E, Vaquero C, Nicholson L, Sack M, Stöger E, Drossard J et al (1999) Rice cell culture as an alternative production system for functional diagnostic and therapeutic antibodies. Transgenic Res 8(6):441–449

    Article  CAS  Google Scholar 

  70. Smith ML, Mason HS, Shuler ML (2002) Hepatitis B surface antigen (HBsAg) expression in plant cell culture: kinetics of antigen accumulation in batch culture and its intracellular form. Biotechnol Bioeng 80:812–822

    Article  CAS  Google Scholar 

  71. Huang TK, McDonald KA (2009) Bioreactor engineering for recombinant protein production in plant cell suspension cultures. Biochem Eng J 45(3):168–184

    Article  CAS  Google Scholar 

  72. Sharma AK, Sharma MK (2009) Plants as bioreactors: recent developments and emerging opportunities. Biotechnol Adv 2:811–832

    Article  CAS  Google Scholar 

  73. Kim NS, Kim TG, Kim OH, Ko EM, Jang YS, Jung ES et al (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 68:263–275

    Article  CAS  Google Scholar 

  74. Shin YJ, Lee NJ, Kima J, An XH, Yang MS, Kwon TH (2010) High-level production of bioactive heterodimeric protein human interleukin-12 in rice. Enzyme Microb Technol 46:347–351

    Article  CAS  Google Scholar 

  75. Springer PS, McCombie WR, Sundaresan V, Martienssen RA (1995) Gene trap tagging of PROLIFERA, an essential MCM2-3-5-like gene in Arabidopsis. Science 268:877–880

    Article  CAS  Google Scholar 

  76. Hepburn AG, Clarke LE, Pearson L, White J (1983) The role of cytosine methylation in the control of nopaline synthase gene expression in a plant tumor. J Mol Appl Genet 2:315–329

    CAS  Google Scholar 

  77. Stam M, De Bruijn R, Kenter S, Van Der Hoorn RAL, Van Blokland R, Mol JNM, Kooter JM (1997) Post-transcriptional silencing of chalcone synthase in Petunia by inverted transgene repeats. Plant J 12:63–82

    Article  CAS  Google Scholar 

  78. Gallie DR, Walbot V (1990) RNA pseudoknot domain of tobacco mosaic virus can functionally substitute for a poly(A) tail in plant and animal cells. Genes Dev 4:1149–1157

    Article  CAS  Google Scholar 

  79. Gallie DR (2002) The 5′-leader of tobacco mosaic virus promotes translation through enhanced recruitment of eIF4F. Nucleic Acids Res 30(15):3401–3411

    Article  CAS  Google Scholar 

  80. Mazur BJ, Chui CF (1985) Sequence of a genomic DNA clone for the small subunit of ribulose bis-phosphate carboxylase-oxygenase from tobacco. Proc Natl Acad Sci 13:2373–2386

    CAS  Google Scholar 

  81. Patel M, Corey AC, Yin LP, Ali S, Taylor WC, Berry JO (2004) Untranslated regions from C4 Amaranth AhRbcS1 mRNAs confer translational enhancement and preferential bundle sheath cell expression in transgenic c4 Flaveria bidentis. Plant Physiol 136:3550–3561

    Article  CAS  Google Scholar 

  82. Patel M, Siegel AJ, Berry JO (2006) Untranslated regions of FbRbcS1 mRNA mediate bundle sheath cell-specific gene expression in leaves of a C4 plant. J Biol Chem 281:25485–25491

    Article  CAS  Google Scholar 

  83. Saxena P, Hsieh Y-C, Alvarado VY, Sainsbury F, Saunders K, Lomonossoff GP, Scholthof HB (2011) Improved foreign gene expression in plants using a virus-encoded suppressor of RNA silencing modified to be developmentally harmless. Plant Biotechnol J 9:703–712

    Article  CAS  Google Scholar 

  84. Verma D, Daniell H (2007) Chloroplast vector systems for biotechnology applications. Plant Physiol 145(4):1129–1143

    Article  CAS  Google Scholar 

  85. Moreira D, Guyader HL, Philippe H (2000) The origin of red algae and the evolution of chloroplasts. Nature 405(6782):69–72

    Article  CAS  Google Scholar 

  86. Gray MW (1999) Evolution of organellar genomes. Curr Opin Genet Dev 9(6):678–687

    Article  CAS  Google Scholar 

  87. Bendich AJ (1987) Why do chloroplasts and mitochondria contain so many copies of their genome? Bioessays 6:279–282

    Article  CAS  Google Scholar 

  88. Heifetz PB, Lers A, Turpin DH, Gillham NW, Boynton JE, Osmond CB (1997) dr and spr/sr mutations of Chlamydomonas reinhardtii affecting D1 protein function and synthesis define two independent steps leading to chronic photoinhibition and confer differential fitness. Plant Cell Environ 20:1145–1157

    Article  CAS  Google Scholar 

  89. Boynton JE, Gillaham NW, Harris EH, Hosler JP, Johnson AM, Jones AR et al (1988) Chloroplast transformation in Chlamydomonas with high velocity microprojectiles. Science 240(4858):1534–1538

    Article  CAS  Google Scholar 

  90. Svab Z, Hajdukiewicz P, Maliga P (1990) Stable transformation of plastids in higher plants. Proc Natl Acad Sci U S A 87:8526–8530

    Article  CAS  Google Scholar 

  91. De Cosa B, Moar W, Lee SB, Miller M, Daniell H (2001) Overexpression of the Bt cry2Aa2 operon in chloroplasts leads to formation of insecticidal crystals. Nat Biotechnol 19:71–74

    Article  Google Scholar 

  92. Bogorad L (2000) Engineering chloroplasts: an alternative site for foreign genes, proteins, reactions and products. Trends Biotechnol 18(6):257–263

    Article  CAS  Google Scholar 

  93. Daniell H, Muthukumar B, Lee SB (2001) Marker free transgenic plants: engineering the chloroplast genome without the use of antibiotic selection. Curr Genet 39:109–116

    Article  CAS  Google Scholar 

  94. Lee SB, Kwon HB, Kwon SJ, Park SC, Jeong MJ, Han SE et al (2003) Accumulation of trehalose within transgenic chloroplasts confers drought tolerance. Mol Breed 11:1–13

    Article  CAS  Google Scholar 

  95. Ruf S, Hermann M, Berger IJ, Carrer H, Bock R (2001) Stable genetic transformation of tomato plastids and expression of a foreign protein in fruit. Nat Biotechnol 19:870–875

    Article  CAS  Google Scholar 

  96. Daniell H (2004) Medical molecular pharming: therapeutic recombinant antibodies, biopharmaceuticals, and edible vaccines in transgenic plants engineered via the chloroplast genome. In: Goodman RM (ed) Encyclopedia of plant and crop science. Marcel Decker, New York, pp 704–710

    Google Scholar 

  97. Doran PM (2006) Foreign protein degradation and instability in plants and plant tissue cultures. Trends Biotechnol 24(9):426–432

    Article  CAS  Google Scholar 

  98. Conrad U, Fiedler U (1998) Compartment-specific accumulation of recombinant immunoglobulins in plant cells: an essential tool for antibody production and immunomodulation of physiological functions and pathogen activity. Plant Mol Biol 38:101–109

    Article  CAS  Google Scholar 

  99. Nuttal J, Vine N, Hadlington JL, Drake P, Frigerio L, Ma JK (2002) ER-resident chaperone interactions with recombinant antibodies in transgenic plants. Eur J Biochem 269:6042–6051

    Article  CAS  Google Scholar 

  100. Petruccelli S, Otegui MS, Lareu F, Tran Dinh O, Fitchette AC, Circosta A et al (2006) A KDEL-tagged monoclonal antibody is efficiently retained in the endoplasmic reticulum in leaves, but is both partially secreted and sorted to protein storage vacuoles in seeds. Plant Biotechnol J 4(5):511–527

    CAS  Google Scholar 

  101. Duwadi K, Chen L, Menassa R, Dhaubhadel S (2015) Identification, characterization and down-regulation of cysteine protease genes in tobacco for use in recombinant protein production. PLoS One 10, e0130556. doi:10.1371/journal.pone.0130556

    Article  CAS  Google Scholar 

  102. Mandal MK, Ahvari H, Schillberg S, Schiermeyer A (2016) Tackling unwanted proteolysis in plant production hosts used for molecular farming. Front Plant Sci 7:267

    Article  Google Scholar 

  103. Pillay P, Kibido T, Plessis M, Vyver C, Beyene G, Vorster BJ et al (2012) Use of transgenic oryzacystatin-I-expressing plants enhances recombinant protein production. Appl Biochem Biotechnol 168:1608–1620

    Article  CAS  Google Scholar 

  104. Pen J, van Ooyen AJJ, van den Elzena PJM, Quaxb WJ, Hoekema A (1993) Efficient production of active industrial enzymes in plants. Ind Crops Prod 1:241–250

    Article  Google Scholar 

  105. Francisco JA, Gawlak AL, Miller M, Bathe J, Russell D, Chace D (1997) Expression and characterization of Bryodin 1 and a Bryodin1-based single chain immunotoxin from tobacco cell culture. Bioconjug Chem 8:708–713

    Article  CAS  Google Scholar 

  106. Ziegler TM, Thomas SR, Danna KJ (2000) Accumulation of a thermostable endo-1,4-β-d-glucanase in the apoplast of Arabidopsis thaliana leaves. Mol Breed 6:37–46

    Article  CAS  Google Scholar 

  107. Xu J, Tan L, Goodrum KJ, Kieliszewski MJ (2007) High-yields and extended serum half-life of human interferon α2b expressed in tobacco cells as arabinogalactan-protein fusions. Biotechnol Bioeng 97(5):997–1008

    Article  CAS  Google Scholar 

  108. Wongsamuth R, Doran PM (1997) Production of monoclonal antibodies by tobacco hairy roots. Biotechnol Bioeng 54:401–415

    Article  CAS  Google Scholar 

  109. LaCount W, An G, Lee JM (1997) The effect of polyvinylpyrrolidone (PVP) on the heavy chain monoclonal antibody production from plant suspension cultures. Biotechnol Lett 19(1):93–96

    Article  CAS  Google Scholar 

  110. James EA, Wang C, Wang Z, Reeves R, Shin JH, Magnuson NS et al (2000) Production and characterization of biologically active human GM-CSF secreted by genetically modified plant cells. Protein Expr Purif 19:131–138

    Article  CAS  Google Scholar 

  111. Makhzoum A, Tahir S, Locke MEO, Trémouillaux-Guiller J, Hefferon K. (2014). An in silico overview on the usefulness of tags and linkers in plant molecular pharming. Plant Science Today 1:201–212

    Google Scholar 

  112. Zhang J, Yun J, Shang Z, Zhang X, Pan B (2009) Design and optimization of a linker for fusion protein construction. Prog Nat Sci 19:1197–1200

    Article  CAS  Google Scholar 

  113. Gomord V, Faye L (2004) Post-translational modification of therapeutic proteins in plants. Curr Opin Plant Biol 7:171–181

    Article  CAS  Google Scholar 

  114. Gomord V, Fitchette AC, 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):564–587

    Article  CAS  Google Scholar 

  115. Faye L, Boulaflous A, Benchabane M, Gomord V, Michaud D (2005) Protein modifications in the plant secretory pathway: current status and practical implications in molecular pharming. Vaccine 23(15):1770–1778

    Article  CAS  Google Scholar 

  116. Gomord V, Chamberlain P, Jefferis R, Faye L (2005) Biopharmaceutical production in plants: problems, solutions and opportunities. Trends Biotechnol 23:559–565

    Article  CAS  Google Scholar 

  117. Saint-Jore-Dupas C, Faye L, Gomord V (2007) From planta to pharma with glycosylation in the toolbox. Trends Biotechnol 25:317–323

    Article  CAS  Google Scholar 

  118. Showalter AM (2001) Arabinogalactan-proteins: structure, expression and function. Cell Mol Life Sci 58:1399–1417

    Article  CAS  Google Scholar 

  119. Qi W, Fong C, Lamport DTA (1991) Gum Arabic glycoprotein is a twisted hairy rope: a new model based on O-galactosyl hydroxyproline as the polysaccharide attachment site. Plant Physiol 96:848–855

    Article  CAS  Google Scholar 

  120. Xu J, Okada S, Tan L, Goodrum KJ, Kopchick JJ, Kieliszewski MJ (2010) Human growth hormone expressed in tobacco cells as an arabinogalactan-protein fusion glycoprotein has a prolonged serum life. Transgenic Res 19(5):849–867

    Article  CAS  Google Scholar 

  121. Hefferon KL (2012) Plant virus expression vectors set the stage as production platforms for biopharmaceutical proteins. Virology 433(1):1–6

    Article  CAS  Google Scholar 

  122. Yusibov V, Streatfield SJ, Kushnir N, Roy G, Padmanaban A (2013) Hybrid viral vectors for vaccine and antibody production in plants. Curr Pharm Des 19(31):5574–5586

    Article  CAS  Google Scholar 

  123. Salazar-González JA, Bañuelos-Hernández B, Rosales-Mendoza S (2015) Current status of viral expression systems in plants and perspectives for oral vaccines development. Plant Mol Biol 87(3):203–217

    Article  CAS  Google Scholar 

  124. Cañizares MC, Nicholson L, Lomonossoff GP (2005) Use of viral vectors for vaccine production in plants. Immunol Cell Biol 83(3):263–270

    Article  CAS  Google Scholar 

  125. Yusibov V, Rabindran S, Commandeur U, Twyman RM, Fischer R (2006) The potential of plant virus vectors for vaccine production. Drugs R& D 7(4):203–217

    Article  CAS  Google Scholar 

  126. Gleba Y, Marillonnet S, Klimyuk V (2004) Engineering viral expression vectors for plants: the ‘full virus’ and the ‘deconstructed virus’ strategies. Curr Opin Plant Biol 7:182–188

    Article  CAS  Google Scholar 

  127. Gleba Y, Klimyuk V, Marillonnet S (2005) Magnifection – a new platform for expressing recombinant vaccines in plants. Vaccine 23(17–18):2042–2048

    Article  CAS  Google Scholar 

  128. Noris E, Poli A, Cojoca R, Rittà M, Cavallo F, Vaglio S et al (2011) A human papillomavirus 8 E7 protein produced in plants is able to trigger the mouse immunsystem and delay the development of skin lesions. Arch Virol 156:587–591

    Article  CAS  Google Scholar 

  129. Huang Z, Phoolcharoen W, Lai H, Piensook K, Cardineau G, Zeitlin L et al (2010) High-level rapid production of full-size monoclonal antibodies in plants by a single-vector DNA replicon system. Biotechnol Bioeng 106(1):9–17

    CAS  Google Scholar 

  130. Musiychuk K, Stephenson N, Bi H, Farrance CE, Orozovic G, Brodelius M et al (2007) A launch vector for the production of vaccine antigens in plants. Influenza Other Respi Viruses 1(1):19–25

    Article  CAS  Google Scholar 

  131. Mett V, Musiychuk K, Bi H, Farrance CE, Horsey A, Ugulava N et al (2008) A plant-produced influenza subunit vaccine protects ferrets against virus challenge. Influenza Other Respi Viruses 2(1):33–40

    Article  CAS  Google Scholar 

  132. Petukhova NV, Gasanova TV, Ivanov PA, Atabekov JG (2014) High-level systemic expression of conserved influenza epitope in plants on the surface of rod-shaped chimeric particles. Viruses 6(4):1789–1800

    Article  CAS  Google Scholar 

  133. Banik S, Mansour AA, Suresh RV, Wykoff-Clary S, Malik M, McCormick AA, Bakshi CS (2015) Development of a multivalent subunit vaccine against tularemia using tobacco mosaic virus (TMV) based delivery system. PLoS One 10(6), e0130858

    Article  CAS  Google Scholar 

  134. Jones RM, Chichester JA, Manceva S, Gibbs SK, Musiychuk K, Shamloul M et al (2015) A novel plant-produced Pfs25 fusion subunit vaccine induces long-lasting transmission blocking antibody responses. Human Vaccines Immunother 11(1):124–132

    Article  Google Scholar 

  135. Sainsbury F, Lavoie P-O, D’Aoust M-A, Vézina L-P, Lomonossoff GP (2008) Expression of multiple proteins using full-length and deleted versions of cowpea mosaic virus RNA-2. Plant Biotechnol J 6:82–92

    CAS  Google Scholar 

  136. Sainsbury F, Thuenemann EC, Lomonossoff GP (2009) pEAQ: versatile expression vectors for easy and quick transient expression of heterologous proteins in plants. Plant Biotechnol J 7:682–693

    Article  CAS  Google Scholar 

  137. Meshcheriakova YA, Saxena P, Lomonossoff GP (2014) Fine-tuning levels of heterologous gene expression in plants by orthogonal variation of the untranslated regions of a nonreplicating transient expression system. Plant Biotechnol J 12(6):718–727

    Article  CAS  Google Scholar 

  138. Sainsbury F, Sack M, Stadlmann J, Quendler H, Fischer R, Lomonossoff GP (2010) Rapid transient production in plants by replicating and non-replicating vectors yields high quality functional anti-HIV antibody. PLoS One 5(11), e13976. doi:10.1371/journal.pone.0013976

    Article  CAS  Google Scholar 

  139. Mardanova ES, Kotlyarov RY, Kuprianov VV, Stepanova LA, Tsybalova LM, Lomonossoff GP, Ravin NV (2016) High immunogenicity of plant-produced candidate influenza vaccine based on the M2e peptide fused to flagellin. Bioengineered 7(1):28–32

    Article  CAS  Google Scholar 

  140. Vardakou M, Sainsbury F, Rigby N, Mulholland F, Lomonossoff GP (2012) Expression of active recombinant human gastric lipase in Nicotiana benthamiana using the CPMV-HT transient expression system. Protein Expr Purif 81(1):69–74

    Article  CAS  Google Scholar 

  141. Thuenemann EC, Meyers AE, Verwey J, Rybicki EP, Lomonossoff GP (2013) A method for rapid production of heteromultimeric protein complexes in plants: assembly of protective bluetongue virus-like particles. Plant Biotechnol J 11(7):839–846

    Article  CAS  Google Scholar 

  142. Regnard GL, Halley-Stott RP, Tanzer FL et al (2010) High level protein expression in plants through the use of a novel autonomously replicating geminivirus shuttle vector. Plant Biotechnol J 8(1):38–46

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Human Genetics Unit, Faculty of Medicine, University of Colombo, Kynsey Road, 00800, Colombo, Sri Lanka

    Sanjeewa Singhabahu

  2. Department of Food Sciences, Cornell University, Ithaca, NY, USA

    Kathleen Hefferon

  3. Department of Biology, The University of Western Ontario, N6A 5B7, London, ON, Canada

    Abdullah Makhzoum

Authors
  1. Sanjeewa Singhabahu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathleen Hefferon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Abdullah Makhzoum
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Kathleen Hefferon or Abdullah Makhzoum .

Editor information

Editors and Affiliations

  1. Department of Botany, Calcutta University, Kolkata, West Bengal, India

    Sumita Jha

Rights and permissions

Reprints and permissions

Copyright information

© 2017 Springer International Publishing AG

About this entry

Cite this entry

Singhabahu, S., Hefferon, K., Makhzoum, A. (2017). Transgenesis and Plant Molecular Pharming. In: Jha, S. (eds) Transgenesis and Secondary Metabolism. Reference Series in Phytochemistry. Springer, Cham. https://doi.org/10.1007/978-3-319-27490-4_21-3

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-27490-4_21-3

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-27490-4

  • Online ISBN: 978-3-319-27490-4

  • eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

Publish with us

Policies and ethics

Chapter history

  1. Latest

    Transgenesis and Plant Molecular Pharming
    Published:
    06 February 2017

    DOI: https://doi.org/10.1007/978-3-319-27490-4_21-3

  2. Transgenesis and Plant Molecular Pharming
    Published:
    29 December 2016

    DOI: https://doi.org/10.1007/978-3-319-27490-4_21-2

  3. Original

    Plant Molecular Pharming
    Published:
    08 October 2016

    DOI: https://doi.org/10.1007/978-3-319-27490-4_21-1

Search

Navigation