Abstract

In recent years, there has been an increased interest of researchers in developing efficient plant heterologous expression systems of proteins for a wide range of applications. It represents an alternative to the traditional strategy utilizing bacterial, yeast, insect or mammalian cells. New techniques of identification and characterization and effective methods of plant genetic transformation allow the range of recombinant protein products to be expanded. Great expectations are associated with the use of plants as bioreactors for the production of specific proteins of therapeutic interest. This strategy offers a number of advantages, the most important being: the possibility of a significant reduction in production costs, the safety of the products obtained and full eukaryotic post-translational modifications of proteins. A group of proteins of special interest is pharmaceuticals, and a number of successful experiments have confirmed the possibility of obtaining heterogeneous proteins with therapeutic potential: monoclonal antibodies, vaccine antigens, and a variety of cytokines. This work is focused on selected recombinant proteins belonging to those groups expression of which was achieved in plant cells. These proteins may be used in the future for therapy or prevention of viral, bacterial or cancer diseases.

References

• 1. Ahmad P., Ashraf M., Younis M., Hu X., Kumar A., Arkam N.A.,Al-Qurainy F.: Role of transgenic plants in agriculture and biopharming.Biotechnol. Adv., 2012; 30: 524-540
  Google Scholar
• 2. Almquist K.C., McLean M.D., Niu Y., Byrne G., Olea-Popelka F.C.,Murrant C., Barclay J., Hall J.C.: Expression of an anti-botulinum toxinA neutralizing single-chain Fv recombinant antibody in transgenictobacco. Vaccine, 2006; 24: 2079-2086
  Google Scholar
• 3. Arlen P.A., Falconer R., Cherukumilli S., Cole A., Cole A.M., OishiK.K., Daniell H.: Field production and functional evaluation of chloroplast-derivedinterferon-α2b. Plant Biotechnol. J., 2007; 5: 511-525
  Google Scholar
• 4. Arlen P.A., Singleton M., Adamovicz J.J., Ding Y., Davoodi-SemiromiA., Daniell H.: Effective plague vaccination via oral delivery ofplant cells expressing F1-V antigens in chloroplasts. Infect. Immun.,2008; 76: 3640-3650
  Google Scholar
• 5. Aziz M.A., Singh S., Anand Kumar P., Bhatnagar R.: Expression ofprotective antigen in transgenic plants: a step towards edible vaccineagainst anthrax. Biochem. Biophys. Res. Commun., 2002; 299: 345-351
  Google Scholar
• 6. Bouquin T., Thomsen M., Nielsen L.K., Green T.H., Mundy J., DziegielM.H.: Human anti-rhesus D IgG1 antibody produced in transgenicplants. Transgenic Res., 2002; 11: 115-122
  Google Scholar
• 7. Brodzik R., Glogowska M., Bandurska K., Okulicz M., Deka D., KoK., van der Linden J., Leusen J.H., Pogrebnyak N., Golovkin M., SteplewskiZ., Koprowski H.: Plant-derived anti-Lewis Y mAb exhibitsbiological activities for efficient immunotherapy against humancancer cells. Proc. Natl. Acad. Sci. USA, 2006; 103: 8804-8809
  Google Scholar
• 8. Brodzik R., Spitsin S., Pogrebnyak N., Bandurska K., PortocarreroC., Andryszak K., Koprowski H., Golovkin M.: Generation of plant-derivedrecombinant DTP subunit vaccine. Vaccine, 2009; 27: 3730-3734
  Google Scholar
• 9. Budzianowski J.: Tytoń – wysokowydajny producent szczepionek.Przegl. Lek., 2010; 67: 1071-1076
  Google Scholar
• 10. Cardi T., Lenzi P., Maliga P.: Chloroplasts as expression platformsfor plant-produced vaccines. Expert Rev. Vaccines, 2010; 9: 893-911
  Google Scholar
• 11. Carter P.J.: Potent antibody therapeutics by design. Nat. Rev.Immunol., 2006; 6: 343-357
  Google Scholar
• 12. Chen H., Shaffer P.L., Huang X., Rose P.E.: Rapid screening ofmembrane protein expression in transiently transfected insect cells.Protein Expr. Purif., 2013; 88: 134-142
  Google Scholar
• 13. Daniell H., Singh N.D., Mason H., Streatfield S.J.: Plant-madevaccine antigens and biopharmaceuticals. Trends Plant Sci., 2009;14: 669-679
  Google Scholar
• 14. Davoodi-Semiromi A., Schreiber M., Nalapalli S., Verma D., SinghN.D., Banks R.K., Chakrabarti D., Daniell H.: Chloroplast-derived vaccineantigens confer dual immunity against cholera and malariaby oral or injectable delivery. Plant Biotechnol. J., 2010; 8: 223-242
  Google Scholar
• 15. De Neve M., De Loose M., Jacobs A., Van Houdt H., Kaluza B., WeidleU., Van Montagu M., Depicker A.: Assembly of an antibody andits derived antibody fragment in Nicotiana and Arabidopsis. TransgenicRes., 1993; 2: 227-237
  Google Scholar
• 16. De Wilde C., De Neve M., De Rycke R., Bruyns A.M., De JaegerG., Van Montagu M., Depicker A., Engler G.: Intact antigen-bindingMAK33 antibody and Fab fragment accumulate in intercellular spacesof Arabidopsis thaliana. Plant Sci., 1996; 114: 233-241
  Google Scholar
• 17. Desai P.N., Shrivastava N., Padh H.: Production of heterologousproteins in plants: strategies for optimal expression. Biotechnol.Adv., 2010; 28: 427-435
  Google Scholar
• 18. Fernandez-San Millan A., Ortigosa S.M., Hervás-Stubbs S., Corral-MartínezP., Seguí-Simarro J.M., Gaétan J., Coursaget P., VeramendiJ.: Human papillomavirus L1 protein expressed in tobaccochloroplasts self-assembles into virus-like particles that are highlyimmunogenic. Plant Biotechnol. J., 2008; 6, 427-441
  Google Scholar
• 19. Fujiwara Y., Aiki Y., Yang L., Takaiwa F., Kosaka A., Tsuji N.M.,Shiraki K., Sekikawa K.: Extraction and purification of human interleukin-10from transgenic rice seeds. Protein Expr. Purif., 2010;72: 125-130
  Google Scholar
• 20. Girard L.S., Fabis M.J., Bastin M., Courtois D., Pétiard V., KoprowskiH.: Expression of a human anti-rabies virus monoclonalantibody in tobacco cell culture. Biochem. Biophys. Res. Commun.,2006; 345: 602-607
  Google Scholar
• 21. Giritch A., Marillonnet S., Engler C., van Eldik G., BottermanJ., Klimyuk V., Gleba Y.: Rapid high-yield expression of full-size IgGantibodies in plants coinfected with noncompeting viral vectors.Proc. Natl. Acad. Sci. USA, 2006; 103: 14701-14706
  Google Scholar
• 22. Gleba Y., Klimyuk V., Marillonnet S.: Magnifection – a new platformfor expressing recombinant vaccines in plants. Vaccine, 2005;23: 2042-2048
  Google Scholar
• 23. Glenz K., Bouchon B., Stehle T., Wallich R., Simon M.M., WarzechaH.: Production of a recombinant bacterial lipoprotein in higherplant chloroplasts. Nat. Biotechnol., 2006; 24: 76-77
  Google Scholar
• 24. Góra-Sochacka A., Radkiewicz P., Napiórkowska B., Sirko A.: Wykorzystaniesystemów roślinnych do produkcji rekombinowanychcytokin. Post. Biochem., 2009; 55: 85-94
  Google Scholar
• 25. Greco R., Michel M., Guetard D., Cervantes-Gonzalez M., PelucchiN., Wain-Hobson S., Sala F., Sala M.: Production of recombinantHIV-1/HBV virus-like particles in Nicotiana tabacum and Arabidopsisthaliana plants for a bivalent plant-based vaccine. Vaccine, 2007;25: 8228-8240
  Google Scholar
• 26. Gul M., Cömert M., Çakmak G.K., Kurtis G., Ugurbas E., Oner M.O.:Effect of erythropoietin on liver regeneration in an experimentalmodel of partial hepatectomy. Int. J. Surg., 2013; 11: 59-63
  Google Scholar
• 27. Hamorsky K.T., Grooms-Williams T.W., Husk A.S., Bennett L.J.,Palmer K.E., Matoba N.: Efficient single tobamoviral vector-basedbioproduction of broadly neutralizing anti-HIV-1 monoclonal antibodyVRC01 in Nicotiana benthamiana plants and utility of VRC01 incombination microbicides. Antimicrob. Agents Chemother., 2013;57: 2076-2086
  Google Scholar
• 28. Haq T.A., Mason H.S., Clements J.D., Arntzen C.J.: Oral immunizationwith a recombinant bacterial antigen produced in transgenicplants. Science, 1995; 268: 714-716
  Google Scholar
• 29. Hassaine G., Deluz C., Tol M.B., Li X.D., Graff A., Vogel H., NuryH.: Large scale expression and purification of the mouse 5-HT3 receptor.Biochim. Biophys. Acta, 2013; 1828: 2544-2552
  Google Scholar
• 30. He J., Lai H., Brock C., Chen Q.: A novel system for rapid andcost-effective production of detection and diagnostic reagents ofWest Nile virus in plants. J. Biomed. Biotechnol., 2012, 2012: 1-10
  Google Scholar
• 31. Hiatt A., Cafferkey R., Bowdish K.: Production of antibodies intransgenic plants. Nature, 1989; 342: 76-78
  Google Scholar
• 32. Hiatt A., Pauly M.: Monoclonal antibodies from plants: a newspeed record. Proc. Natl. Acad. Sci. USA, 2006; 103: 14645-14646
  Google Scholar
• 33. Horn M.E., Woodard S.L., Howard J.A.: Plant molecular farming:systems and products. Plant Cell Rep., 2004; 22: 711-720
  Google Scholar
• 34. James E.A., Wang C., Wang Z., Reeves R., Shin J.H., MagnusonN.S., Lee J.M.: Production and characterization of biologically activehuman GM-CSF secreted by genetically modified plant cells. ProteinExpr. Purif., 2000; 19: 131-138
  Google Scholar
• 35. Jani D., Meena L.S., Rizwan-ul-Haq Q.M., Singh Y., Sharma A.K.,Tyagi A.K.: Expression of cholera toxin B subunit in transgenic tomatoplants. Transgenic Res., 2002; 11: 447-454
  Google Scholar
• 36. Jez J., Castilho A., Grass J., Vorauer-Uhl K., Sterovsky T., AltmannF., Steinkellner H.: Expression of functionally active sialylated humanerythropoietin in plants. Biotechnol. J., 2013; 8: 371-382
  Google Scholar
• 37. Kolenda P., Litwiniuk M.: Kontynuacja terapii trastuzumabempo operacyjnym leczeniu przerzutu do mózgu – opis przypadku.Wsp. Onkol., 2010; 14: 393-396
  Google Scholar
• 38. Komarova T.V., Kosorukov V.S., Frolova O.Y., Petrunia I.V., SkrypnikK.A., Gleba Y.Y., Dorokhov Y.L.: Plant-made trastuzumab (herceptin)inhibits HER2/Neu+ cell proliferation and retards tumor growth.PLoS One, 2011; 6: e17541
  Google Scholar
• 39. Koya, V., Moayeri M., Leppla S.H., Daniell H.: Plant-based vaccine:mice immunized with chloroplast-derived anthrax protectiveantigen survive anthrax lethal toxin challenge. Infect. Immun.,2005; 73: 8266-8274
  Google Scholar
• 40. Lai H., Engle M., Fuchs A., Keller T., Johnson S., Gorlatov S., DiamondM.S., Chen Q.: Monoclonal antibody produced in plants efficientlytreats West Nile virus infection in mice. Proc. Natl. Acad. Sci.USA, 2010; 107: 2419-2424
  Google Scholar
• 41. Leader B., Baca Q.J., Golan D.E.: Protein therapeutics: a summaryand pharmacological classification. Nat. Rev. Drug Discov.,2008; 7: 21-39
  Google Scholar
• 42. Lee J.H., Kim N.S., Kwon T.H., Jang Y.S., Yang M.S.: Increasedproduction of human granulocyte-macrophage colony stimulatingfactor (hGM-CSF) by the addition of stabilizing polymer in plantsuspension cultures. J. Biotechnol., 2002; 96: 205-211
  Google Scholar
• 43. Lee J.H., Park D.Y., Lee K.J., Kim Y.K., So Y.K., Ryu J.S., Oh S.H., HanY.S., Ko K., Choo Y.K., Park S.J., Brodzik R., Lee K.K., Oh D.B., HwangK.A., Koprowski H., Lee Y.S., Ko K.: Intracellular reprogramming ofexpression, glycosylation, and function of a plant-derived antiviraltherapeutic monoclonal antibody. PLoS One, 2013, 8: e68772
  Google Scholar
• 44. Lewko W.M., Oldham R.K.: Cytokines, W: Principles of CancerBiotherapy, red.: Oldham R.K., Dillman R.O., Springer Netherlands,Nowy Jork, 2009, 155-276
  Google Scholar
• 45. Lowther W., Lorick K., Lawrence S.D., Yeow W.S.: Expression ofbiologically active human interferon alpha 2 in Aloe vera. TransgenicRes., 2012; 21: 1349-1357
  Google Scholar
• 46. Luchakivskaya Y., Kishchenko O., Gerasymenko I., OlevinskayaZ., Simonenko Y., Spivak M., Kuchuk M.: High-level expression ofhuman interferon alpha-2b in transgenic carrot (Daucus carota L.)plants. Plant Cell Rep., 2011; 30: 407-415
  Google Scholar
• 47. Łoś J.M., Węgrzyn G.: Enterokrwotoczne szczepy Escherichiacoli (EHEC) i bakteriofagi kodujące toksyny Shiga. Post. Mikrobiol.,2011; 50: 175-190
  Google Scholar
• 48. Łoś-Rycharska E., Czerwionka-Szaflarska M.: Biegunki rotawirusowe– dlaczego warto im zapobiegać. Prz. Gastroenterol., 2011;6: 60-68
  Google Scholar
• 49. Magnuson N.S., Linzmaier P.M., Reeves R., An G., HayGlass K.,Lee J.M.: Secretion of biologically active human interleukin-2 andinterleukin-4 from genetically modified tobacco cells in suspensionculture. Protein Expr. Purif., 1998; 13: 45-52
  Google Scholar
• 50. Mahmoud K.: Recombinant protein production: strategic technologyand a vital research tool. Res. J. Cell Mol. Biol., 2007; 1: 9-22
  Google Scholar
• 51. Mason H.S., Haq T.A.; Clements J.D.; Arntzen C.J.: Edible vaccineprotects mice against Escherichia coli heat-labile enterotoxin (LT): potatoesexpressing a synthetic LT-B gene. Vaccine, 1998; 16: 1336-1343
  Google Scholar
• 52. Matsumoto S., Ishii A., Ikura K., Ueda M., Sasaki R.: Expression ofhuman erythropoietin in cultured tobacco cells. Biosci. Biotechnol.Biochem., 1993; 57: 1249-1252
  Google Scholar
• 53. Matsumura T., Itchoda N., Tsunemitsu H.: Production of immunogenicVP6 protein of bovine group A rotavirus in transgenicpotato plants. Arch. Virol., 2002; 147: 1263-1270
  Google Scholar
• 54. Morens D.M., Folkers G.K., Fauci A.S.: The challenge of emergingand re-emerging infectious diseases. Nature, 2004; 430: 242-249
  Google Scholar
• 55. Nair A.M., Tsai Y.T., Shah K.M., Shen J., Weng H., Zhou J., SunX., Saxena R., Borrelli J.Jr., Tang L.: The effect of erythropoietin onautologous stem cell-mediated bone regeneration. Biomaterials,2013; 34: 7364-7371
  Google Scholar
• 56. Nakanishi K., Narimatsu S., Ichikawa S., Tobisawa Y., KurohaneK., Niwa Y., Kobayashi H., Imai Y.: Production of hybrid-IgG/IgAplantibodies with neutralizing activity against Shiga toxin 1. PLoSOne, 2013; 8: e80712
  Google Scholar
• 57. O’Hara J.M., Whaley K., Pauly M., Zeitlin L., Mantis N.J.: Plant–based expression of a partially humanized neutralizing monoclonalIgG directed against an immunodominant epitope on the ricin toxinA subunit. Vaccine, 2012; 30: 1239-1243
  Google Scholar
• 58. Ohya K., Itchoda N., Ohashi K., Onuma M., Sugimoto C., MatsumuraT.: Expression of biologically active human tumor necrosisfactor-alpha in transgenic potato plant. J. Interferon Cytokine Res.,2002; 22: 371-378
  Google Scholar
• 59. Olinger G.G.Jr., Pettitt J., Kim D., Working C., Bohorov O., BratcherB., Hiatt E., Hume S.D., Johnson A.K., Morton J., Pauly M., WhaleyK.J., Lear C.M., Biggins J.E., Scully C., Hensley L., Zeitlin L.: Delayedtreatment of Ebola virus infection with plant-derived monoclonalantibodies provides protection in rhesus macaques. Proc. Natl. Acad.Sci. USA, 2012; 109: 18030-18035
  Google Scholar
• 60. Oszvald M., Kang T.J., Tomoskozi S., Jenes B., Kim T.G., Cha Y.S.,Tamas L., Yang M.S.: Expression of cholera toxin B subunit in transgenicrice endosperm. Mol. Biotechnol., 2008; 40: 261-268
  Google Scholar
• 61. Pogrebnyak N., Markley K., Smirnov Y., Brodzik R., BandurskaK., Koprowski H., Golovkin M.: Collard and cauliflower as a base forproduction of recombinant antigens. Plant Sci., 2006; 171: 677-685
  Google Scholar
• 62. Ramessar K., Rademacher T., Sack M., Stadlmann J., Platis D.,Stiegler G., Labrou N., Altmann F., Ma J., Stöger E., Capell T., ChristouP.: Cost-effective production of a vaginal protein microbicideto prevent HIV transmission. Proc. Natl. Acad. Sci. USA, 2008; 105:3727-3732
  Google Scholar
• 63. Rodríguez M., Pujol M., Pérez L., Gavilondo J.V., Garrido G., AyalaM., Pérez M., Bequet-Romero M., Cabrera G., Ramos O., HernándezI., González E.M., Huerta V., Sánchez B., Mateo C. i wsp.: Transgenicplants of Nicotiana tabacum L. express aglycosylated monoclonalantibody with antitumor activity. Biotecnol. Apl., 2013; 30: 157-161
  Google Scholar
• 64. Rosales-Mendoza S., Soria-Guerra R.E., López-Revilla R., Moreno-FierrosL., Alpuche-Solís A.G.: Ingestion of transgenic carrotsexpressing the Escherichia coli heat-labile enterotoxin B subunit protectsmice against cholera toxin challenge. Plant Cell Rep., 2008;27: 79-84
  Google Scholar
• 65. Rosenberg Y., Sack M., Montefiori D., Forthal D., Mao L., Hernandez-AbantoS., Urban L., Landucci G., Fischer R., Jiang X.: Rapidhigh-level production of functional HIV broadly neutralizing monoclonal antibodies in transient plant expression systems. PLoSOne, 2013; 8: e58724
  Google Scholar
• 66. Ruhlman T., Ahangari R., Devine A., Samsam M., Daniell H.:Expression of cholera toxin B-proinsulin fusion protein in lettuceand tobacco chloroplasts – oral administration protects against developmentof insulitis in non-obese diabetic mice. Plant Biotechnol.J., 2007; 5: 495-510
  Google Scholar
• 67. Rybicki E.P.: Plant-made vaccines for humans and animals. PlantBiotechnol. J., 2010; 8: 620-637
  Google Scholar
• 68. Sack M., Paetz A., Kunert R., Bomble M., Hesse F., Stiegler G.,Fischer R., Katinger H., Stoeger E., Rademacher T.: Functional analysisof the broadly neutralizing human anti-HIV-1 antibody 2F5produced in transgenic BY-2 suspension cultures. FASEB J., 2007;21: 1655-1664
  Google Scholar
• 69. Sakhno L.O., Krasko O.Y., Olevinska Z.M., Spivak M.Y., KuchukM.V.: Creation of transgenic Brassica napus L. plants expressing humanalpha 2b interferon gene. Tsitol. Genet., 2012; 46: 12-18
  Google Scholar
• 70. Sharp J.M., Doran P.M.: Effect of bacitracin on growth and monoclonalantibody production by tobacco hairy roots and cell suspensions.Biotechnol. Bioprocess Eng., 1999; 4: 253-258
  Google Scholar
• 71. Shchelkunov S.N., Salyaev R.K., Pozdnyakov S.G., RekoslavskayaN..I, Nesterov A.E., Ryzhova T.S., Sumtsova V.M., PakovaN.V., Mishutina U.O., Kopytina T.V., Hammond R.W.: Immunogenicityof a novel, bivalent, plant-based oral vaccine against hepatitisB and human immunodeficiency viruses. Biotechnol. Lett.,2006; 28: 959-967
  Google Scholar
• 72. Shin Y.J., Hong S.Y., Kwon T.H., Jang Y.S., Yang M.S.: High levelof expression of recombinant human granulocyte-macrophage colonystimulating factor in transgenic rice cell suspension culture.Biotechnol. Bioeng., 2003; 82: 778-783
  Google Scholar
• 73. Sirko A., Vaněk T., Góra-Sochacka A., Radkiewicz P.: Recombinantcytokines from plants. Int. J. Mol. Sci., 2011; 12: 3536-3552
  Google Scholar
• 74. Swiech K., Picanço-Castro V., Covas D.T.: Human cells: new platformfor recombinant therapeutic protein production. Protein Expr.Purif., 2012; 84: 147-153
  Google Scholar
• 75. Tackaberry E.S, Dudani A.K.; Prior F., Tocchi M., Sardana R.,Altosaar I., Ganz P.R.: Development of biopharmaceuticals in plantexpression systems: cloning, expression and immunological reactivityof human cytomegalovirus glycoprotein B (UL55) in seeds oftransgenic tobacco. Vaccine, 1999; 17: 3020-3029
  Google Scholar
• 76. Tayal V., Kalra B.S.: Cytokines and anti-cytokines as therapeutics– an update. Eur. J. Pharmacol., 2008; 579: 1-12
  Google Scholar
• 77. Thanavala Y., Mahoney M., Pal S., Scott A., Richter L., NatarajanN., Goodwin P., Arntzen C.J., Mason H.S.: Immunogenicity inhumans of an edible vaccine for hepatitis B. Proc. Natl. Acad. Sci.USA, 2005; 102: 3378-3382
  Google Scholar
• 78. Tokuhara D., Álvarez B., Mejima M., Hiroiwa T., Takahashi Y.,Kurokawa S., Kuroda M., Oyama M., Kozuka-Hata H., Nochi T., SagaraH., Aladin F., Marcotte H., Frenken L.G., Iturriza-Gómara M. i wsp.:Rice-based oral antibody fragment prophylaxis and therapy againstrotavirus infection. J. Clin. Invest., 2013; 123: 3829-3838
  Google Scholar
• 79. Tremblay R., Wang D., Jevnikar A.M., Ma S.: Tobacco, a highlyefficient green bioreactor for production of therapeutic proteins.Biotechnol. Adv., 2010; 28: 214-221
  Google Scholar
• 80. Triguero A., Cabrera G., Cremata J.A., Yuen C.T., Wheeler J.,Ramírez N.I.: Plant-derived mouse IgG monoclonal antibody fusedto KDEL endoplasmic reticulum-retention signal is N-glycosylatedhomogeneously throughout the plant with mostly high-mannose–type N-glycans. Plant Biotechnol. J., 2005; 3: 449-457
  Google Scholar
• 81. Vézina L.P., Faye L., Lerouge P., D’Aoust M.A., Marquet-Blouin E.,Burel C., Lavoie P.O., Bardor M., Gomord V.: Transient co-expressionfor fast and high-yield production of antibodies with human-like N–glycans in plants. Plant Biotechnol. J., 2009; 7: 442-455
  Google Scholar
• 82. Virágh M., Vörös D., Kele Z., Kovács L., Fizil A., Lakatos G., MarótiG., Batta G., Vágvölgyi C., Galgóczy L.: Production of a defensin-likeantifungal protein NFAP from Neosartorya fischeri in Pichia pastorisand its antifungal activity against filamentous fungal isolates fromhuman infections. Protein Expr. Purif., 2014; 94: 79-84
  Google Scholar
• 83. Wang X., Brandsma M., Tremblay R., Maxwell D., Jevnikar A.M.,Huner N., Ma S.: A novel expression platform for the production ofdiabetes-associated autoantigen human glutamic acid decarboxylase(hGAD65). BMC Biotechnol., 2008; 8: 87
  Google Scholar
• 84. Wang Y., Deng H., Zhang X., Xiao H., Jiang Y., Song Y., Fang L.,Xiao S., Zhen Y., Chen H.: Generation and immunogenicity of Japaneseencephalitis virus envelope protein expressed in transgenic rice.Biochem. Biophys. Res. Commun., 2009; 380: 292-297
  Google Scholar
• 85. Wirz H., Sauer-Budge A.F., Briggs J., Sharpe A., Shu S., Sharon A.:Automated production of plant-based vaccines and pharmaceuticals.J. Lab. Autom., 2012; 17: 449-457
  Google Scholar
• 86. Xu K., Evans D.B., Carrin G., Aguilar-Rivera A.M., Musgrove P.,Evans T.: Protecting households from catastrophic health spending.Health Aff., 2007; 26: 972-983
  Google Scholar
• 87. Yusibov V., Streatfield S.J., Kushnir N.: Clinical development ofplant-produced recombinant pharmaceuticals: vaccines, antibodiesand beyond. Hum. Vaccin., 2011; 7: 313-321
  Google Scholar
• 88. Zhang C., Allegretti M., Vonck J., Langer J.D., Marcia M., Peng G.,Michel H.: Production of fully assembled and active Aquifex aeolicus F1FOATP synthase in Escherichia coli. Biochim. Biophys. Acta, 2014; 1840: 34-40
  Google Scholar
• 89. Zhou F., Badillo-Corona J.A., Karcher D., Gonzalez-Rabade N.,Piepenburg K., Borchers A.M., Maloney A.P., Kavanagh T.A., GrayJ.C., Bock R.: High-level expression of human immunodeficiencyvirus antigens from the tobacco and tomato plastid genomes. PlantBiotechnol. J., 2008; 6: 897-913
  Google Scholar
• 90. Zhou Y.X, Lee M.Y., Ng J.M., Chye M.L., Yip W.K., Zee S.Y., LamE.: A truncated hepatitis E virus ORF2 protein expressed in tobaccoplastids is immunogenic in mice. World J. Gastroenterol., 2006;12: 306-312
  Google Scholar
• 91. Zhu Z., Hughes K.W., Huang L., Sun B., Liu C., Li Y., Hou Y., Li X.:Expression of human α-interferon cDNA in transgenic rice plants.Plant Cell Tissue Organ Cult., 1994; 36: 197-204
  Google Scholar

Full text