Antibodies from plants for bionanomaterials

Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology

Volumn 9, Issue 6, 2017, Pages

  Edgue, Gueven ^a   Twyman, Richard M ^b   Beiss, Veronique ^a   Fischer, Rainer ^a,c   Sack, Markus ^a  

^a RWTH AACHEN UNIVERSITY   (Germany)

^b TRM Ltd   (United Kingdom)

^c FRAUNHOFER INSTITUTE FOR MOLECULAR BIOLOGY AND APPLIED ECOLOGY IME   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

DNA SEQUENCES; MAMMALS; MANUFACTURE; VIRUSES;

ADAPTIVE IMMUNE RESPONSE; INDUSTRIAL SCALE; LABORATORY TECHNOLOGIES; MAMMALIAN CELLS; NANOTECHNOLOGY APPLICATIONS; SAFE PRODUCTION; SUPRAMOLECULAR STRUCTURE; TRANSIENT EXPRESSION;

ANTIBODIES;

ANTIBODY; NANOMATERIAL; PLANTIBODY;

AGROBACTERIUM TUMEFACIENS; ANTIBODY PRODUCTION; GOOD MANUFACTURING PRACTICE; NANOMEDICINE; NEXT GENERATION SEQUENCING; NONHUMAN; PLANT; PRIORITY JOURNAL; REVIEW; TRANSIENT EXPRESSION; ANIMAL; CHEMISTRY; HUMAN; METABOLISM; PROTEIN DOMAIN; TRANSLATIONAL RESEARCH;

ANIMALS; HUMANS; NANOMEDICINE; NANOSTRUCTURES; PLANTIBODIES; PROTEIN DOMAINS; TRANSLATIONAL MEDICAL RESEARCH;

EID: 85017391776     PISSN: 19395116     EISSN: 19390041     Source Type: Journal    
DOI: 10.1002/wnan.1462     Document Type: Review

References (180)

1. Stoger E, Sack M, Fischer R, Christou P. Plantibodies: applications, advantages and bottlenecks. Curr Opin Biotechnol 2002, 13:161–166.
2. Stoger E, Sack M, Nicholson L, Fischer R, Christou P. Recent progress in plantibody technology. Curr Pharm Des 2005, 11:2439–2457.
3. Ma JK, Drake PM, Christou P. The production of recombinant pharmaceutical proteins in plants. Nat Rev Genet 2003, 4:794–805.
4. Stoger E, Fischer R, Moloney M, Ma JK. Plant molecular pharming for the treatment of chronic and infectious diseases. Annu Rev Plant Biol 2014, 65:743–768.
5. Muyldermans S, Baral TN, Retamozzo VC, De Baetselier P, De Genst E, Kinne J, Leonhardt H, Magez S, Nguyen VK, Revets H, et al. Camelid immunoglobulins and nanobody technology. Vet Immunol Immunopathol 2009, 128:178–183.
6. Geyer CR, McCafferty J, Dübel S, Bradbury AR, Sidhu SS. Recombinant antibodies and in vitro selection technologies. Methods Mol Biol 2012, 901:11–32.
7. Larrick JW, Alfenito MR, Scott JK, Parren PW, Burton DR, Bradbury AR, Lemere CA, Messer A, Huston JS, Carter PJ, et al. Antibody engineering & therapeutics 2016, The Antibody Society's Annual Meeting, December 11–15, 2016, San Diego, CA. MAbs 2016, 8:1425–1434.
8. Schroeder HW, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol 2010, 125:S41–S52.
9. Lefranc MP. Antibody informatics: IMGT, the International ImMunoGeneTics Information System. Microbiol Spectr 2014, 2:2.
10. Alamyar E, Giudicelli V, Duroux P, Lefranc MP. Antibody V and C domain sequence, structure, and interaction analysis with special reference to IMGT®. Methods Mol Biol 2014, 1131:337–381.
11. Ducancel F, Muller BH. Molecular engineering of antibodies for therapeutic and diagnostic purposes. MAbs 2012, 4:445–457.
12. Bradbury A, Plückthun A. Reproducibility: standardize antibodies used in research. Nature 2015, 518:27–29.
13. Patron NJ, Orzaez D, Marillonnet S, Warzecha H, Matthewman C, Youles M, Raitskin O, Leveau A, Farré G, Rogers C, et al. Standards for plant synthetic biology: a common syntax for exchange of DNA parts. New Phytol 2015, 208:13–19.
14. Liao HX, Levesque MC, Nagel A, Dixon A, Zhang R, Walter E, Parks R, Whitesides J, Marshall DJ, Hwang KK, et al. High-throughput isolation of immunoglobulin genes from single human B cells and expression as monoclonal antibodies. J Virol Methods 2009, 158:171–179.
15. Hiatt A, Cafferkey R, Bowdish K. Production of antibodies in transgenic plants. Nature 1989, 342:76–78.
16. Düring K, Hippe S, Kreuzaler F, Schell J. Synthesis and self-assembly of a functional monoclonal antibody in transgenic Nicotiana tabacum. Plant Mol Biol 1990, 15:281–293.
17. Owen M, Gandecha A, Cockburn B, Whitelam G. Synthesis of a functional anti-phytochrome single-chain Fv protein in transgenic tobacco. Biotechnology 1992, 10:790–794.
18. Tavladoraki P, Benvenuto E, Trinca S, De Martinis D, Cattaneo A, Galeffi P. Transgenic plants expressing a functional single-chain Fv antibody are specifically protected from virus attack. Nature 1993, 366:469–472.
19. Artsaenko O, Peisker M, zur Nieden U, Fiedler U, Weiler EW, Müntz K, Conrad U. Expression of a single-chain Fv antibody against abscisic acid creates a wilty phenotype in transgenic tobacco. Plant J 1995, 8:745–750.
20. Fiedler U, Conrad U. High-level production and long-term storage of engineered antibodies in transgenic tobacco seeds. Biotechnology 1995, 13:1090–1093.
21. Ma JK, Hiatt A, Hein M, Vine ND, Wang F, Stabila P, van Dolleweerd C, Mostov K, Lehner T. Generation and assembly of secretory antibodies in plants. Science 1995, 268:716–719.
22. Voss A, Niersbach M, Hain R, Hirsch HJ, Liao YC, Kreuzaler F, Fischer R. Reduced virus infectivity in N. tabacum secreting a TMV-specific full-size antibody. Mol Breed 1995, 1:39–50.
23. Bruyns AM, De Jaeger G, De Neve M, De Wilde C, Van Montagu M, Depicker A. Bacterial and plant-produced scFv proteins have similar antigen-binding properties. FEBS Lett 1996, 386:5–10.
24. Marschall AL, Dübel S, Böldicke T. Specific in vivo knockdown of protein function by intrabodies. MAbs 2015, 7:1010–1035.
25. Cao T, Heng BC. Intracellular antibodies (intrabodies) versus RNA interference for therapeutic applications. Ann Clin Lab Sci 2005, 35:227–229.
26. Stocks MR. Intrabodies: production and promise. Drug Discov Today 2004, 9:960–966.
27. Fischer R, Schumann D, Zimmermann S, Drossard J, Sack M, Schillberg S. Expression and characterization of bispecific single-chain Fv fragments produced in transgenic plants. Eur J Biochem 1999, 262:810–816.
28. Schillberg S, Zimmermann S, Voss A, Fischer R. Apoplastic and cytosolic expression of full-size antibodies and antibody fragments in Nicotiana tabacum. Transgenic Res 1999, 8:255–263.
29. Cervera M, Esteban O, Gil M, Gorris MT, Martínez MC, Peña L, Cambra M. Transgenic expression in citrus of single-chain antibody fragments specific to Citrus tristeza virus confers virus resistance. Transgenic Res 2010, 19:1001–1015.
30. Franconi R, Roggero P, Pirazzi P, Arias FJ, Desiderio A, Bitti O, Pashkoulov D, Mattei B, Bracci L, Masenga V, et al. Functional expression in bacteria and plants of an scFv antibody fragment against tospoviruses. Immunotechnology 1999, 4:189–201.
31. Fecker LF, Kaufmann A, Commandeur U, Commandeur J, Koenig R, Burgermeister W. Expression of single-chain antibody fragments (scFv) specific for beet necrotic yellow vein virus coat protein or 25 kDa protein in Escherichia coli and Nicotiana benthamiana. Plant Mol Biol 1996, 32:979–986.
32. Fecker LF, Koenig R, Obermeier C. Nicotiana benthamiana plants expressing beet necrotic yellow vein virus (BNYVV) coat protein-specific scFv are partially protected against the establishment of the virus in the early stages of infection and its pathogenic effects in the late stages of infection. Arch Virol 1997, 142:1857–1863.
33. Orecchia M, Nölke G, Saldarelli P, Dell'Orco M, Uhde-Holzem K, Sack M, Martelli G, Fischer R, Schillberg S. Generation and characterization of a recombinant antibody fragment that binds to the coat protein of grapevine leafroll-associated virus 3. Arch Virol 2008, 153:1075–1084.
34. Boonrod K, Galetzka D, Nagy PD, Conrad U, Krczal G. Single-chain antibodies against a plant viral RNA-dependent RNA polymerase confer virus resistance. Nat Biotechnol 2004, 22:856–862.
35. Xiao XW, Chu PWG, Frenkel MJ, Tabe LM, Shukla DD, Hanna PJ, Higgins TJV, Müller WJ, Ward CW. Antibody-mediated improved resistance to ClYVV and PVY infections in transgenic tobacco plants expressing a single-chain variable region antibody. Mol Breed 2000, 6:421–431.
36. Le Gall F, Bove JM, Garnier M. Engineering of a single-chain variable-fragment (scFv) antibody specific for the stolbur phytoplasma (Mollicute) and its expression in Escherichia coli and tobacco plants. Appl Environ Microbiol 1998, 64:4566–4572.
37. Peschen D, Li HP, Fischer R, Kreuzaler F, Liao YC. Fusion proteins comprising a Fusarium-specific antibody linked to antifungal peptides protect plants against a fungal pathogen. Nat Biotechnol 2004, 22:732–738.
38. Li HP, Zhang JB, Shi RP, Huang T, Fischer R, Liao YC. Engineering Fusarium head blight resistance in wheat by expression of a fusion protein containing a Fusarium-specific antibody and an antifungal peptide. Mol Plant Microbe Interact 2008, 21:1242–1248.
39. Yuan Q, Hu W, Pestka JJ, He SY, Hart LP. Expression of a functional antizearalenone single-chain Fv antibody in transgenic Arabidopsis plants. Appl Environ Microbiol 2000, 66:3499–3505.
40. Yajima W, Verma SS, Shah S, Rahman MH, Liang Y, Kav NN. Expression of anti-sclerotinia scFv in transgenic Brassica napus enhances tolerance against stem rot. Nat Biotechnol 2010, 27:816–821.
41. van Engelen FA, Schouten A, Molthoff JW, Roosien J, Salinas J, Dirkse WG, Schots A, Bakker J, Gommers FJ, Jongsma MA, et al. Coordinate expression of antibody subunit genes yields high levels of functional antibodies in roots of transgenic tobacco. Plant Mol Biol 1994, 26:1701–1710.
42. Eto J, Suzuki Y, Ohkawa H, Yamaguchi I. Anti-herbicide single-chain antibody expression confers herbicide tolerance in transgenic plants. FEBS Lett 2003, 550:179–184.
43. Almquist KC, Niu Y, McLean MD, Mena FL, Yau KY, Brown K, Brandle JE, Hall JC. Immunomodulation confers herbicide resistance in plants. Plant Biotechnol J 2004, 2:189–197.
44. Weiss Y, Shulman A, Ben Shir I, Keinan E, Wolf S. Herbicide-resistance conferred by expression of a catalytic antibody in Arabidopsis thaliana. Nat Biotechnol 2006, 24:713–717.
45. Baum TJ, Hiatt A, Parrott WA, Pratt LH, Hussey RS. Expression in tobacco of a functional monoclonal antibody specific to stylet secretions of the root-knot nematode. Mol Plant Microbe Interact 1996, 9:382–387.
46. Rosso MN, Schouten A, Roosien J, Borst-Vrenssen T, Hussey RS, Gommers FJ, Bakker J, Schots A, Abad P. Expression and functional characterization of a single chain Fv antibody directed against secretions involved in plant nematode infection process. Biochem Biophys Res Commun 1996, 18:255–263.
47. Phillips J, Artsaenko O, Fiedler U, Horstmann C, Mock HP, Müntz K, Conrad U. Seed-specific immunomodulation of abscisic acid activity induces a developmental switch. EMBO J 1997, 16:4489–4496.
48. Shimada N, Suzuki Y, Nakajima M, Conrad U, Murofushi N, Yamaguchi I. Expression of a functional single-chain antibody against GA24/19 in transgenic tobacco. Biosci Biotechnol Biochem 1999, 63:779–783.
49. Suzuki Y, Mizuno T, Urakami E, Yamaguchi I, Asami T. Immunomodulation of bioactive gibberellin confers gibberellin-deficient phenotypes in plants. Plant Biotechnol J 2008, 6:355–367.
50. Urakami E, Yamaguchi I, Asami T, Conrad U, Suzuki Y. Immunomodulation of gibberellin biosynthesis using an anti-precursor gibberellin antibody confers gibberellin- deficient phenotypes. Planta 2008, 228:863–873.
51. ten Hoopen P, Hunger A, Müller A, Hause B, Kramell R, Wasternack C, Rosahl S, Conrad U. Immunomodulation of jasmonate to manipulate the wound response. J Exp Bot 2007, 58:2525–2535.
52. Putalun W, Taura F, Qing W, Matsushita H, Tanaka H, Shoyama Y. Anti-solasodine glycoside single-chain Fv antibody stimulates biosynthesis of solasodine glycoside in plants. Plant Cell Rep 2003, 22:344–349.
53. Sakamoto S, Putalun W, Pongkitwitoon B, Juengwatanatrakul T, Shoyama Y, Tanaka H, Morimoto S. Modulation of plumbagin production in Plumbago zeylanica using a single-chain variable fragment antibody against plumbagin. Plant Cell Rep 2012, 31:103–110.
54. Zábrady M, Hrdinová V, Müller B, Conrad U, Hejátko J, Janda L. Targeted in vivo inhibition of specific protein-protein interactions using recombinant antibodies. PLoS One 2014, 9:e109875.
55. Miroshnichenko S, Tripp J, Uz N, Neumann D, Conrad U, Manteuffel R. Immunomodulation of function of small heat shock proteins prevents their assembly into heat stress granules and results in cell death at sublethal temperatures. Plant J 2005, 41:269–281.
56. Vaquero C, Sack M, Chandler J, Drossard J, Schuster F, Monecke M, Schillberg S, Fischer R. Transient expression of a tumor-specific single-chain fragment and a chimeric antibody in tobacco leaves. Proc Natl Acad Sci USA 1999, 96:11128–11133.
57. Stoger E, Sack M, Perrin Y, Vaquero C, Torres E, Twyman RM, Christou P, Fischer R. Practical considerations for pharmaceutical antibody production in different crop systems. Mol Breed 2002, 9:149–158.
58. Ma JK, Drossard J, Lewis D, Altmann F, Boyle J, Christou P, Cole T, Dale P, van Dolleweerd CJ, Isitt V, et al. Regulatory approval and a first-in-human phase I clinical trial of a monoclonal antibody produced in transgenic tobacco plants. Plant Biotechnol J 2015, 13:1106–1120.
59. Sack M, Rademacher T, Spiegel H, Boes A, Hellwig S, Drossard J, Stoger E, Fischer R. From gene to harvest: insights into upstream process development for the GMP production of a monoclonal antibody in transgenic tobacco plants. Plant Biotechnol J 2015, 13:1094–1105.
60. Sack M, Paetz A, Kunert R, Bomble M, Hesse F, Stiegler G, Fischer R, Katinger H, Stoeger E, Rademacher T. Functional analysis of the broadly neutralizing human anti-HIV-1 antibody 2 F5 produced in transgenic BY-2 suspension cultures. FASEB J 2007, 21:1655–1664.
61. van Dolleweerd CJ, Teh AY, Banyard AC, Both L, Lotter-Stark HC, Tsekoa T, Phahladira B, Shumba W, Chakauya E, Sabeta CT, et al. Engineering, expression in transgenic plants and characterisation of E559, a rabies virus-neutralising monoclonal antibody. J Infect Dis 2014, 210:200–208.
62. Both L, van Dolleweerd C, Wright E, Banyard AC, Bulmer-Thomas B, Selden D, Altmann F, Fooks AR, Ma JK. Production, characterization, and antigen specificity of recombinant 62-71-3, a candidate monoclonal antibody for rabies prophylaxis in humans. FASEB J 2013, 27:2055–2065.
63. Lee JH, Park DY, Lee KJ, Kim YK, So YK, Ryu JS, Oh SH, Han YS, Ko K, Choo YK, et al. Intracellular reprogramming of expression, glycosylation, and function of a plant-derived antiviral therapeutic monoclonal antibody. PLoS One 2013, 8:e68772.
64. Ma JK, Hikmat BY, Wycoff K, Vine ND, Chargelegue D, Yu L, Hein MB, Lehner T. Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans. Nat Med 1998, 4:601–606.
65. Ma JK, Lehner T, Stabila P, Fux CI, Hiatt A. Assembly of monoclonal antibodies with IgG1 and IgA heavy chain domains in transgenic tobacco plants. Eur J Immunol 1994, 24:131–138.
66. Hiatt A, Pauly M, Whaley K, Qiu X, Kobinger G, Zeitlin L. The emergence of antibody therapies for Ebola. Hum Antibodies 2015, 23:49–56.
67. Zeitlin L, Olmsted SS, Moench TR, Co MS, Martinell BJ, Paradkar VM, Russell DR, Queen C, Cone RA, Whaley KJ. A humanized monoclonal antibody produced in transgenic plants for immunoprotection of the vagina against genital herpes. Nat Biotechnol 1998, 16:1361–1364.
68. Semenyuk EG, Orlova IV, Stremovskii OA, Balandin TG, Nosov AM, Bur'yanov Y, Deev SM. Transgenic tobacco plants produce miniantibodies against human ferritin. Dokl Biochem Biophys 2002, 384:176–178.
69. Ehsani P, Meunier A, Nato F, Jafari A, Nato A, Lafaye P. Expression of anti-human IL-4 and IL-6 scFvs in transgenic tobacco plants. Plant Mol Biol 2003, 52:17–29.
70. Rodriguez M, Ramirez NI, Ayala M, Freyre F, Perez L, Triguero A, Mateo C, Selman-Housein G, Gavilondo JV, Pujol M. Transient expression in tobacco leaves of an aglycosylated recombinant antibody against the epidermal growth factor receptor. Biotechnol Bioeng 2005, 89:188–194.
71. Francisco JA, Gawlak SL, Miller M, Bathe J, Russell D, Chace D, Mixan B, Zhao L, Fell HP, Siegall CB. Expression and characterization of bryodin 1 and a bryodin 1-based single-chain immunotoxin from tobacco cell culture. Bioconjug Chem 1997, 8:708–713.
72. Hull AK, Criscuolo CJ, Mett V, Groen H, Steeman W, Westra H, Chapman G, Legutki B, Baillie L, Yusibov V. Human-derived, plant-produced monoclonal antibody for the treatment of anthrax. Vaccine 2005, 23:2082–2086.
73. Makvandi-Nejad S, McLean MD, Hirama T, Almquist KC, Mackenzie CR, Hall JC. Transgenic tobacco plants expressing a dimeric single-chain variable fragment (scFv) antibody against Salmonella enterica serotype paratyphi B. Transgenic Res 2005, 14:785–792.
74. Ko K, Tekoah Y, Rudd PM, Harvey DJ, Dwek RA, Spitsin S, Hanlon CA, Rupprecht C, Dietzschold B, Golovkin M, Koprowski H. Function and glycosylation of plant-derived antiviral monoclonal antibody. Proc Natl Acad Sci USA 2003, 100, 8013–8018.
75. Ko K, Steplewski Z, Glogowska M, Koprowski H. Inhibition of tumor growth by plant-derived mAb. Proc Natl Acad Sci USA 2005, 102:7026–7030.
76. McCormick AA, Kumagai MH, Hanley K, Turpen TH, Hakim I, Grill LK, Tuse D, Levy S, Levy R. Rapid production of specific vaccines for lymphoma by expression of the tumor-derived single-chain Fv epitopes in tobacco plants. Proc Natl Acad Sci USA 1999, 96:703–708.
77. Bendandi M, Marillonnet S, Kandzia R, Thieme F, Nickstadt A, Herz S, Fröde R, Inogés S, Lòpez-Dìaz de Cerio A, Soria E, et al. Rapid, high-yield production in plants of individualized idiotype vaccines for non-Hodgkin's lymphoma. Ann Oncol 2010, 21:2420–2427.
78. Chargelegue D, Drake PM, Obregon P, Prada A, Fairweather N, Ma JK. Highly immunogenic and protective recombinant vaccine candidate expressed in transgenic plants. Infect Immun 2005, 73:5915–5922.
79. Bouquin T, Thomsen M, Nielsen LK, Green TH, Mundy J, Hanefeld DM. Human anti-rhesus D IgG1 antibody produced in transgenic plants. Transgenic Res 2002, 11:115–122.
80. De Neve M, De Loose M, Jacobs A, Van Houdt H, Kaluza B, Weidle U, Van Montagu M, Depicker A. Assembly of an antibody and its derived antibody fragment in Nicotiana and Arabidopsis. Transgenic Res 1993, 2:227–237.
81. De Wilde C, De Rycke R, Beeckman T, De Neve M, Van Montagu M, Engler G, Depicker A. Accumulation pattern of IgG antibodies and Fab fragments in transgenic Arabidopsis thaliana plants. Plant Cell Physiol 1998, 39:639–646.
82. Kathuria S, Sriraman R, Nath R, Sack M, Pal R, Artsaenko O, Talwar GP, Fischer R, Finnern R. Efficacy of plant-produced recombinant antibodies against HCG. Hum Reprod 2002, 17:2054–2061.
83. Floss DM, Sack M, Stadlmann J, Rademacher T, Scheller J, Stöger E, Fischer R, Conrad U. Biochemical and functional characterization of anti-HIV antibody-ELP fusion proteins from transgenic plants. Plant Biotechnol J 2008, 6:379–391.
84. Floss DM, Sack M, Arcalis E, Stadlmann J, Quendler H, Rademacher T, Stoger E, Scheller J, Fischer R, Conrad U. Influence of elastin-like peptide fusions on the quantity and quality of a tobacco-derived human immunodeficiency virus-neutralizing antibody. Plant Biotechnol J 2009, 7:899–913.
85. Conrad U, Plagmann I, Malchow S, Sack M, Floss DM, Kruglov AA, Nedospasov SA, Rose-John S, Scheller J. ELPylated anti-human TNF therapeutic single-domain antibodies for prevention of lethal septic shock. Plant Biotechnol J 2011, 9:22–31.
86. Peyret H, Gehin A, Thuenemann EC, Blond D, El Turabi A, Beales L, Clarke D, Gilbert RJ, Fry EE, Stuart DI, et al. Tandem fusion of hepatitis B core antigen allows assembly of virus-like particles in bacteria and plants with enhanced capacity to accommodate foreign proteins. PLoS One 2015, 10:e0120751.
87. Ramírez N, Rodríguez M, Ayala M, Cremata J, Pérez M, Martínez A, Linares M, Hevia Y, Páez R, Valdés R, et al. Expression and characterization of an anti-(hepatitis B surface antigen) glycosylated mouse antibody in transgenic tobacco (Nicotiana tabacum) plants and its use in the immunopurification of its target antigen. Biotechnol Appl Biochem 2003, 38:223–230.
88. Vanier G, Hempel F, Chan P, Rodamer M, Vaudry D, Maier UG, Lerouge P, Bardor M. Biochemical characterization of human anti-Hepatitis B monoclonal antibody produced in the microalgae Phaeodactylum tricornutum. PLoS One 2015, 10:e0139282.
89. Mainieri D, Morandini F, Maîtrejean M, Saccani A, Pedrazzini E, Alessandro V. Protein body formation in the endoplasmic reticulum as an evolution of storage protein sorting to vacuoles: insights from maize γ-zein. Front Plant Sci 2014, 5:331.
90. Torrent M, Llop-Tous I, Ludevid MD. Protein body induction: a new tool to produce and recover recombinant proteins in plants. Methods Mol Biol 2009, 483:193–208.
91. Reuter L, Ritala A, Linder M, Joensuu J. Novel hydrophobin fusion tags for plant-produced fusion proteins. PLoS One 2016, 11:e0164032.
92. Arcalis E, Ibl V, Peters J, Melnik S, Stoger E. The dynamic behavior of storage organelles in developing cereal seeds and its impact on the production of recombinant proteins. Front Plant Sci 2014, 5:439.
93. Kapila J, De Rycke R, van Montagu M, Angenon G. An Agrobacterium-mediated transient gene expression system for intact leaves. Plant Sci 1997, 122:101–108.
94. Canizares MC, Nicholson L, Lomonossoff GP. Use of viral vectors for vaccine production in plants. Immunol Cell Biol 2005, 83:263–270.
95. Yusibov V, Rabindran S, Commandeur U, Twyman RM, Fischer R. The potential of plant virus vectors for vaccine production. Drugs R&D 2006, 7:203–217.
96. Zischewski J, Sack M, Fischer R. Overcoming low yields of plant-made antibodies by a protein engineering approach. Biotechnol J 2016, 11:107–116.
97. 36. Spiegel H, Boes A, Voepel N, Beiss V, Edgue G, Rademacher T, Sack M, Schillberg S, Reimann A, Fischer R. Application of a scalable plant transient gene expression platform for malaria vaccine development. Front Plant Sci 2015, 6:1169.
98. Landry N, Ward BJ, Trépanier S, Montomoli E, Dargis M, Lapini G, Vézina LP. Preclinical and clinical development of plant-made virus-like particle vaccine against avian H5N1 influenza. PLoS One 2010, 5:e15559.
99. Pandey A, Singh N, Sambhara S, Mittal SK. Egg-independent vaccine strategies for highly pathogenic H5N1 influenza viruses. Hum Vaccin 2010, 6:178–188.
100. Rappuoli R, Dormitzer PR. Influenza: options to improve pandemic preparation. Science 2012, 336:1531–1533.
101. Benvenuto E, Ordas RJ, Tavazza R, Ancora G, Biocca S, Cattaneo A, Galeffi P. ‘Phytoantibodies’: a general vector for the expression of immunoglobulin domains in transgenic plants. Plant Mol Biol 1991, 17:865–874.
102. Nicholson L, Gonzalez-Melendi P, van Dolleweerd C, Tuck H, Perrin Y, Ma JK, Fischer R, Christou P, Stoger E. A recombinant multimeric immunoglobulin expressed in rice shows assembly-dependent subcellular localization in endosperm cells. Plant Biotechnol J 2005, 3:115–127.
103. Zimmermann S, Schillberg S, Liao YC, Fischer R. Intracellular expression of TMV-specific single-chain Fv fragments leads to improved virus resistance in Nicotiana tabacum. Mol Breed 1998, 4:369–379.
104. Chen YD, Chen TA. Expression of engineered antibodies in plants: a possible tool for spiroplasma and phytoplasma disease control. Phytopathology 1998, 88:1367–1371.
105. Bouaziz D, Ayadi M, Bidani A, Rouis S, Nouri-Ellouz O, Jellouli R, Drira N, Gargouri-Bouzid R. A stable cytosolic expression of VH antibody fragment directed against PVY NIa protein in transgenic potato plant confers partial protection against the virus. Plant Sci 2009, 176:489–496.
106. Safarnejad MR, Fischer R, Commandeur U. Recombinant-antibody-mediated resistance against Tomato yellow leaf curl virus in Nicotiana benthamiana. Arch Virol 2009, 154:457–467.
107. Hendy S, Chen ZC, Barker H, Santa Cruz S, Chapman S, Torrance L, Cockburn W, Whitelam GC. Rapid production of single-chain Fv fragments in plants using a potato virus X episomal vector. J Immunol Methods 1999, 231:137–146.
108. Ziegler A, Cowan GH, Torrance L, Ross HA, Davies HV. Facile assessment of cDNA constructs for expression of functional antibodies in plants using the potato virus X vector. Mol Breed 2000, 6:327–335.
109. Vaquero C, Sack M, Schuster F, Finnern R, Drossard J, Schumann D, Reimann A, Fischer R. A carcinoembryonic antigen-specific diabody produced in tobacco. FASEB J 2002, 16:408–410.
110. Verch T, Yusibov V, Koprowski H. Expression and assembly of a full-length monoclonal antibody in plants using a plant virus vector. J Immunol Methods 1998, 220:69–75.
111. Marillonnet S, Thoeringer C, Kandzia R, Klimyuk V, Gleba Y. Systemic Agrobacterium tumefaciens-mediated transfection of viral replicons for efficient transient expression in plants. Nat Biotechnol 2005, 23:718–723.
112. Gleba Y, Marillonnet S, Klimyuk V. Engineering viral expression vectors for plants: the ‘full virus’ and the ‘deconstructed virus’ strategies. Curr Opin Plant Biol 2004, 7:182–188.
113. Gleba Y, Klimyuk V, Marillonnet S. Magnifection—a new platform for expressing recombinant vaccines in plants. Vaccine 2005, 23:2042–2048.
114. Regnard GL, Halley-Stott RP, Tanzer FL, Hitzeroth II, Rybicki EP. High level protein expression in plants through the use of a novel autonomously replicating geminivirus shuttle vector. Plant Biotechnol J 2010, 8:38–46.
115. Lai H, He J, Engle M, Diamond MS, Chen Q. Robust production of virus-like particles and monoclonal antibodies with geminiviral replicon vectors in lettuce. Plant Biotechnol J 2012, 10:95–104.
116. Borisjuk NV, Borisjuk LG, Logendra S, Petersen F, Gleba Y, Raskin I. Production of recombinant proteins in plant root exudates. Nat Biotechnol 1999, 17:466–469.
117. Komarnytsky S, Borisjuk NV, Borisjuk LG, Alam MZ, Raskin I. Production of recombinant proteins in tobacco guttation fluid. Plant Physiol 2000, 124:927–933.
118. Sharp JM, Doran PM. Characterization of monoclonal antibody fragments produced by plant cells. Biotechnol Bioeng 2001, 73:338–346.
119. Sharp JM, Doran PM. Strategies for enhancing monoclonal antibody accumulation in plant cell and organ cultures. Biotechnol Prog 2001, 17:979–992.
120. Firek S, Draper J, Owen MR, Gandecha A, Cockburn B, Whitelam GC. Secretion of a functional single-chain Fv protein in transgenic tobacco plants and cell suspension cultures. Plant Mol Biol 1993, 23:861–870.
121. LaCount W, An G, Lee JM. The effect of polyvinylpyrrolidone (PVP) on the heavy chain monoclonal antibody production from plant suspension cultures. Biotechnol Lett 1997, 19:93–96.
122. Fischer R, Liao YC, Drossard J. Affinity-purification of a TMV-specific recombinant full-size antibody from a transgenic tobacco suspension culture. J Immunol Methods 1999, 226:1–10.
123. Artsaenko O, Kettig B, Fiedler U, Conrad U, During K. Potato tubers as a biofactory for recombinant antibodies. Mol Breed 1998, 4:313–319.
124. De Wilde C, Peeters K, Jacobs A, Peck I, Depicker A. Expression of antibodies and Fab fragments in transgenic potato plants: a case study for bulk production in crop plants. Mol Breed 2002, 9:271–282.
125. Khoudi H, Laberge S, Ferullo JM, Bazin R, Darveau A, Castonguay Y, Allard G, Lemieux R, Vezina LP. Production of a diagnostic monoclonal antibody in perennial alfalfa plants. Biotechnol Bioeng 1999, 64:135–143.
126. Stoger E, Vaquero C, Torres E, Sack M, Nicholson L, Drossard J, Williams S, Keen D, Perrin Y, Christou P, et al. Cereal crops as viable production and storage systems for pharmaceutical scFv antibodies. Plant Mol Biol 2000, 42:583–590.
127. Schünmann PH, Coia G, Waterhouse PM. Biopharming the SimpliRED™ HIV diagnostic reagent in barley, potato and tobacco. Mol Breed 2002, 9:113–121.
128. Perrin Y, Vaquero C, Gerrard I, Sack M, Drossard J, Stoger E, Christou P, Fischer R. Transgenic pea seeds as bioreactors for the production of a single-chain Fv fragment (scFV) antibody used in cancer diagnosis and therapy. Mol Breed 2000, 6:345–352.
129. Torres E, Vaquero C, Nicholson L, Sack M, Stoger E, Drossard J, Christou P, Fischer R, Perrin Y. Rice cell culture as an alternative production system for functional diagnostic and therapeutic antibodies. Transgenic Res 1999, 8:441–449.
130. Hood EE, Woodard SL, Horn ME. Monoclonal antibody manufacturing in transgenic plants—myths and realities. Curr Opin Biotechnol 2002, 13:630–635.
131. Juárez P, Presa S, Espí J, Pineda B, Antón MT, Moreno V, Buesa J, Granell A, Orzaez D. Neutralizing antibodies against rotavirus produced in transgenically labelled purple tomatoes. Plant Biotechnol J 2012, 10:341–352.
132. Decker EL, Reski R. The moss bioreactor. Curr Opin Plant Biol 2004, 7:166–170.
133. Gasdaska JR, Spencer D, Dickey L. Advantages of therapeutic protein production in the aquatic plant Lemna. BioProcess J 2003, 2003:49–56.
134. Weintraub JA, Hilton JF, White JM, Hoover CI, Wycoff KL, Yu L, Larrick JW, Featherstone JD. Clinical trial of a plant-derived antibody on recolonization of mutans streptococci. Caries Res 2005, 39:241–250.
135. Cross JW. The rise and fall of a duckweed biotechnology firm: what can it tell us? ISCDRA 2015, 83–88.
136. McCormick AA, Reddy S, Reinl SJ, Cameron TI, Czerwinkski DK, Vojdani F, Hanley KM, Garger SJ, White EL, Novak J, et al. Plant-produced idiotype vaccines for the treatment of non-Hodgkin's lymphoma: safety and immunogenicity in a phase I clinical study. Proc Natl Acad Sci USA 2008, 105:10131–10136.
137. Sparrow PAC, Irwin JA, Dale PJ, Twyman RM, Ma JKC. Pharma-Planta: road testing the developing regulatory guidelines for plant-made pharmaceuticals. Transgenic Res 2007, 16:147–161.
138. Spök A, Twyman RM, Fischer R, Ma JKC, Sparrow PAC. Evolution of a regulatory framework for pharmaceuticals derived from genetically modified plants. Trends Biotechnol 2008, 26:506–517.
139. Qiu X, Wong G, Audet J, Bello A, Fernando L, Alimonti JB, Fausther-Bovendo H, Wei H, Aviles J, Hiatt E, et al. Reversion of advanced Ebola virus disease in nonhuman primates with ZMapp. Nature 2014, 514:47–53.
140. Na W, Park N, Yeom M, Song D. Ebola outbreak in Western Africa 2014: what is going on with Ebola virus? Clin Exp Vaccine Res 2015, 4:17–22.
141. Gelvin SB. Agrobacterium and plant genes involved in T-DNA transfer and integration. Annu Rev Plant Physiol Plant Mol Biol 2000, 51:223–256.
142. Gelvin SB. Agrobacterium-mediated plant transformation: the biology behind the gene jockeying tool. Microbiol Mol Biol Rev 2003, 67:16–37.
143. Nester EW. Agrobacterium: nature's genetic engineer. Front Plant Sci 2014, 5:730.
144. Lacroix B, Citovsky V. Transfer of DNA from bacteria to eukaryotes. MBio 2016, 7:e00863-16.
145. Peyret H, Lomonossoff GP. The pEAQ vector series: the easy and quick way to produce recombinant proteins in plants. Plant Mol Biol 2013, 83:51–58.
146. Shah KH, Almaghrabi B, Bohlmann H. Comparison of expression vectors for transient expression of recombinant proteins in plants. Plant Mol Biol Report 2013, 31:1529–1538.
147. Watson MR, Lin YF, Hollwey E, Dodds RE, Meyer P, McDowall KJ. An improved binary vector and Escherichia coli strain for Agrobacterium tumefaciens-mediated plant transformation. G3 (Bethesda) 2016, 6:2195–2201.
148. Banta L M, Montenegro M. Agrobacterium and plant biotechnology. In: Tzfira T, Citovsky V. Agrobacterium: From Biology to Biotechnology. New York: Springer 2008, 73–147.
149. Baron C, Domke N, Beinhofer M, Hapfelmeier S. Elevated temperature differentially affects virulence, VirB protein accumulation, and T-pilus formation in different Agrobacterium tumefaciens and Agrobacterium vitis strains. J Bacteriol 2001, 183:6852–6861.
150. Dillen W, De Clercq J, Kapila J, Zambre M, Van Montagu M, Angenon G. The effect of temperature on Agrobacterium tumefaciens-mediated gene transfer to plants. Plant J 1997, 12:1459–1463.
151. Fullner KJ, Nester EW. Temperature affects the T-DNA transfer machinery of Agrobacterium tumefaciens. J Bacteriol 1996, 178:1498–1504.
152. Filipe V, Hawe A, Jiskoot W. Critical evaluation of nanoparticle tracking analysis (NTA) by NanoSight for the measurement of nanoparticles and protein aggregates. Pharm Res 2010, 27:796–810.
153. Engin S, Fichtner D, Wedlich D, Fruk L. SNAP-tag as a tool for surface immobilization. Curr Pharm Des 2013, 19:5443–5448.
154. Niesen J, Sack M, Seidel M, Fendel R, Barth S, Fischer R, Stein C. SNAP-tag technology: a useful tool to determine affinity constants and other functional parameters of novel antibody fragments. Bioconjug Chem 2016, 27:1931–1941.
155. Lee KL, Twyman RM, Fiering S, Steinmetz NF. Virus-based nanoparticles as platform technologies for modern vaccines. Wiley Interdiscip Rev Nanomed Nanobiotechnol 2016, 8:544–578.
156. Marsian J, Lomonossoff GP. Molecular pharming—VLPs made in plants. Curr Opin Biotechnol 2016, 37:201–206.
157. Smolenska L, Roberts IM, Learmonth D, Porter AJ, Harris WJ, Wilson TM, Santa CS. Production of a functional single chain antibody attached to the surface of a plant virus. FEBS Lett 1998, 441:379–382.
158. Werner S, Marillonnet S, Hause G, Klimyuk V, Gleba Y. Immunoabsorbent nanoparticles based on a tobamovirus displaying protein A. Proc Natl Acad Sci USA 2006, 103:17678–17683.
159. Hundleby PAC, Sack M, Twyman RM. Biosafety, risk assessment and regulation of molecular farming. In: Kermode A, Fraser S, Jiang L, eds. Molecular Pharming: Applications, Challenges and Emerging Areas. Mannheim, Germany: Wiley-VCH; 2017(in press).
160. Gomord V, Fitchette AC, Menu-Bouaouiche L, Saint-Jore-Dupas C, Plasson C, Michaud D, Faye L. Plant-specific glycosylation patterns in the context of therapeutic protein production. Plant Biotechnol J 2010, 8:564–587.
161. Fischer R, Schillberg S, Hellwig S, Twyman RM, Drossard J. GMP issues for plant-derived recombinant proteins. Biotechnol Adv 2012, 30:434–439.
162. Fischer R, Buyel JF, Schillberg S, Twyman RM. Molecular farming in plants: the long road to the market. Biotechnol Agr For 2014, 68:27–41.
163. Loos A, Steinkellner H. Plant glyco-biotechnology on the way to synthetic biology. Front Plant Sci 2014, 5:423.
164. Decker EL, Parsons J, Reski R. Glyco-engineering for biopharmaceutical production in moss bioreactors. Front Plant Sci 2014, 5:346.
165. Castilho A, Steinkellner H. Glyco-engineering in plants to produce human-like N-glycan structures. Biotechnol J 2012, 7:1088–1098.
166. Cox KM, Sterling JD, Regan JT, Gasdaska JR, Frantz KK, Peele CG, Black A, Passmore D, Moldovan-Loomis C, Srinivasan M, et al. Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor. Nat Biotechnol 2006, 24:1591–1597.
167. Bortesi L, Fischer R. The CRISPR/Cas9 system for plant genome editing and beyond. Biotechnol Adv 2015, 33:41–52.
168. Garabagi F, Gilbert E, Loos A, McLean MD, Hall JC. Utility of the P19 suppressor of gene-silencing protein for production of therapeutic antibodies in Nicotiana expression hosts. Plant Biotechnol J 2012, 10:1118–1128.
169. Hehle VK, Lombardi R, van Dolleweerd CJ, Paul MJ, Di Micco P, Morea V, Benvenuto E, Donini M, Ma JK. Site-specific proteolytic degradation of IgG monoclonal antibodies expressed in tobacco plants. Plant Biotechnol J 2015, 13:235–245.
170. Komarnytsky S, Borisjuk N, Yakoby N, Garvey A, Raskin I. Cosecretion of protease inhibitor stabilizes antibodies produced by plant roots. Plant Physiol 2006, 141:1185–1193.
171. Mandal MK, Fischer R, Schillberg S, Schiermeyer A. Inhibition of protease activity by antisense RNA improves recombinant protein production in Nicotiana tabacum cv. Bright Yellow 2 (BY-2) suspension cells. Biotechnol J 2014, 9:1065–1073.
172. Buyel JF, Fischer R, Twyman RM. Extraction and downstream processing of plant-derived recombinant proteins. Biotechnol Adv 2015, 33:902–913.
173. Lomonossoff GP, D'Aoust MA. Plant-produced biopharmaceuticals: a case of technical developments driving clinical deployment. Science 2016, 353:1237–1240.
174. Nandi S, Kwong AT, Holtz BR, Erwin RL, Marcel S, McDonald KA. Techno-economic analysis of a transient plant-based platform for monoclonal antibody production. MAbs 2016, 8:1456–1466.
175. Tusé D, Tu T, McDonald KA. Manufacturing economics of plant-made biologics: case studies in therapeutic and industrial enzymes. BioMed Res Intl 2014, 2014:256135.
176. Walwyn DR, Huddy SM, Rybicki EP. Techno-economic analysis of horseradish peroxidase production using a transient expression system in Nicotiana benthamiana. Appl Biochem Biotechnol 2015, 175:841–854.
177. Morrison C, Lähteenmäki R. Public biotech in 2015—the numbers. Nat Biotechnol 2016, 34:709–715.
178. Lizotte PH, Wen AM, Sheen MR, Fields J, Rojanasopondist P, Steinmetz NF, Fiering S. In situ vaccination with cowpea mosaic virus nanoparticles suppresses metastatic cancer. Nat Nanotechnol 2016, 11:295–303.
179. Lebel MÈ, Chartrand K, Leclerc D, Lamarre A. Plant viruses as nanoparticle-based vaccines and adjuvants. Vaccines (Basel) 2015, 3:620–637.
180. Wu Z, Chen K, Yildiz I, Dirksen A, Fischer R, Dawson PE, Steinmetz NF. Development of viral nanoparticles for efficient intracellular delivery. Nanoscale 2012, 4:3567–3576.