Chloroplasts as expression platforms for plant-produced vaccines

Expert Review of Vaccines

Volumn 9, Issue 8, 2010, Pages 893-911

  Cardi, Teodoro ^a,b   Lenzi, Paolo ^c   Maliga, Pal ^d  

^a CNR   (Italy)

^b ISTITUTO NAZIONALE DELLA NUTRIZIONE   (Italy)

^c JOHN INNES CENTRE   (United Kingdom)

^d RUTGERS UNIVERSITY   (United States)

Author keywords

Chlamydomonas; chloroplast; genetic transformation; lettuce; oral delivery; plastid; production platform; subunit vaccine; tobacco; transplastomic plant

Indexed keywords

RECOMBINANT ANTIGEN; RECOMBINANT VACCINE;

CHLAMYDOMONAS REINHARDTII; CHLOROPLAST; GENE EXPRESSION; GENE SILENCING; GENE TECHNOLOGY; NONHUMAN; OPERON; PLANT; PLASTID GENOME; POLLEN; PRIORITY JOURNAL; PROKARYOTE; REVIEW; TOBACCO; TRANSGENE; VACCINE PRODUCTION; BIOSYNTHESIS; BIOTECHNOLOGY; GENETICS; HUMAN; METABOLISM; PROCEDURES; TRANSGENIC PLANT;

BIOTECHNOLOGY; CHLAMYDOMONAS REINHARDTII; CHLOROPLASTS; GENE EXPRESSION; HUMANS; PLANTS, GENETICALLY MODIFIED; TOBACCO; VACCINES, SYNTHETIC;

EID: 77955242155     PISSN: 14760584     EISSN: 17448395     Source Type: Journal    
DOI: 10.1586/erv.10.78     Document Type: Review

References (176)

1. Barta A, Sommergruber K, Thompson D, Hartmuth K, Matzke MA, Matzke AJM. The expression of a nopaline synthase - human growth hormone chimaeric gene in transformed tobacco and sunflower callus tissue. Plant Mol. Biol. 6(5), 347-357 (1986).
2. Mason HS, Lam DM, Arntzen CJ. Expression of hepatitis B surface antigen in transgenic plants. Proc. Natl Acad. Sci. USA 89(24), 11745-11749 (1992).
3. Daniell H, Singh ND, Mason H, Streatfield SJ. Plant-made vaccine antigens and biopharmaceuticals. Trends Plant Sci. 14(12), 669-679 (2009).
4. Arntzen C, Plotkin S, Dodet B. Plant- derived vaccines and antibodies: potential and limitations. Vaccine 23(15), 1753-1756 (2005).
5. Yusibov V, Rabindran S. Recent progress in the development of plant derived vaccines. Expert Rev. Vaccines 7(8), 1173-1183 (2008).
6. Saint-Jore-Dupas C, Faye L, Gomord V. From planta to pharma with glycosylation in the toolbox. Trends Biotechnol. 25(7), 317-323 (2007).
7. Rybicki EP. Plant-produced vaccines: promise and reality. Drug Discov. Today 14(1-2), 16-24 (2009).
8. Lutz KA, Azhagiri AK, Tungsuchat-Huang T, Maliga P. A guide to choosing vectors for transformation of the plastid genome of higher plants. Plant Physiol. 145(4), 1201-1210 (2007).
9. Maliga P. Plastid transformation in higher plants. Ann. Rev. Plant Biol. 55, 289-313 (2004).
10. Verma D, Daniell H. Chloroplast vector systems for biotechnology applications. Plant Physiol. 145(4), 1129-1143 (2007).
11. Blowers AD, Bogorad L, Shark KB, Sanford JC. Studies on Chlamydomonas chloroplast transformation: foreign DNA can be stably maintained in the chromosome. Plant Cell 1(1), 123-132 (1989).
12. Boynton JE, Gillham NW, Harris EH et al. Chloroplast transformation in Chlamydomonas with high velocity microprojectiles. Science 240, 1534-1537 (1988).
13. Svab Z, Hajdukiewicz P, Maliga P. Stable transformation of plastids in higher plants. Proc. Natl Acad. Sci. USA 87(21), 8526-8530 (1990).
14. Svab Z, Maliga P. High-frequency plastid transformation in tobacco by selection for a chimeric aadA gene. Proc. Natl Acad. Sci. USA 90, 913-917 (1993).
15. Koop H-U, Herz S, Golds T, Nickelsen J. The genetic transformation of plastids. Top. Curr. Genet. 19, 457-510 (2007).
16. Mayfield SP, Manuell AL, Chen S et al. Chlamydomonas reinhardtii chloroplasts as protein factories. Curr. Opin. Biotechnol. 18(2), 126-133 (2007).
17. Surzycki R, Greenham K, Kitayama K et al. Factors effecting expression of vaccines in microalgae. Biologicals 37(3), 133-138 (2009).
18. Pyke K. Plastid biogenesis and differentiation. Top. Curr. Genet. 19, 1-28 (2007).
19. Bock R. Structure, function, and inheritance of plastid genomes. Top. Curr. Genet. 19, 29-63 (2007).
20. Bollenbach T, Schuster G, Portnoy V, Stern D. Processing, degradation, and polyadenylation of chloroplast transcripts. Top. Curr. Genet. 19, 175-211 (2007).
21. Liere K, Borner T. Transcription and transcriptional regulation in plastids. Top. Curr. Genet. 19, 121-174 (2007).
22. Marin-Navarro J, Manuell A, Wu J, Mayfield SP. Chloroplast translation regulation. Photosynth. Res. 94(2), 359-374 (2007).
23. Peled-Zehavi H, Danon A. Translation and translational regulation in chloroplasts. Top. Curr. Genet. 19, 249-281 (2007).
24. Schmitz-Linneweber C, Barkan A. RNA splicing and RNA editing in chloroplasts. Top. Curr. Genet. 19, 213-248 (2007).
25. Brosch M, Krause K, Falk J, Krupinska K. Analysis of gene expression in amyloplasts of potato tubers. Planta 227, 91-99 (2007).
26. Kahlau S, Bock R. Plastid transcriptomics and translatomics of tomato fruit development and chloroplast-to- chromoplast differentiation: chromoplast gene expression largely serves the production of a single protein. Plant Cell 20(4), 856-874 (2008).
27. Valkov VT, Scotti N, Kahlau S et al. Genome-wide analysis of plastid gene expression in potato leaf chloroplasts and tuber amyloplasts: transcriptional and posttranscriptional control. Plant Physiol. 150(4), 2030-2044 (2009).
28. Day A, Madesis P. DNA replication, recombination, and repair in plastids. Top. Curr. Genet. 19, 65-119 (2007).
29. Maliga P. Engineering the plastid genome of higher plants. Curr. Opin. Plant Biol. 5, 164-172 (2002).
30. Maliga P. Progress toward commercialization of plastid transformation technology. Trends Biotechnol. 21, 20-28 (2003).
31. Lossl A, Bohmert K, Harloff H, Eibl C, Muhlbauer S, Koop H-U. Inducible trans-activation of plastid transgenes: expression of the R. eutropha phb operon in transplastomic tobacco. Plant Cell Physiol. 46(9), 1462-1471 (2005).
32. Magee A, Coyne S, Murphy D, Horvath E, Medgyesy P, Kavanagh T. T7 RNA polymerase-directed expression of an antibody fragment transgene in plastids causes a semi-lethal pale-green seedling phenotype. Transgenic Res. 13(4), 325-337 (2004).
33. Magee AM, Horvath EM, Kavanagh TA. Pre-screening plastid transgene expression cassettes in Escherichia coli may be unreliable as a predictor of expression levels in chloroplast-transformed plants. Plant Sci. 166(6), 1605-1611 (2004).
34. McBride KE, Schaaf DJ, Daley M, Stalker DM. Controlled expression of plastid transgenes in plants based on a nuclear DNA-encoded and plastid- targeted T7 RNA polymerase. Proc. Natl Acad. Sci. USA 91(15), 7301-7305 (1994).
35. Kuroda H, Maliga P. Sequences downstream of the translation initiation codon are important determinants of translation efficiency in chloroplasts. Plant Physiol. 125(1), 430-436 (2001).
36. Gray B, Ahner B, Hanson M. Extensive homologous recombination between introduced and native regulatory plastid DNA elements in transplastomic plants. Transgenic Res. 18(4), 559-572 (2009).
37. McCabe MS, Klaas M, Gonzalez- Rabade N et al. Plastid transformation of high-biomass tobacco variety Maryland Mammoth for production of human immunodeficiency virus type 1 (HIV-1) p24 antigen. Plant Biotechnol. J. 6, 914-929 (2008).
38. Zhou F, Badillo-Corona JA, Karcher D et al. High-level expression of human immunodeficiency virus antigens from the tobacco and tomato plastid genomes. Plant Biotechnol. J. 6(9), 897-913 (2008).
39. Heifetz PB. Genetic engineering of the chloroplast. Biochimie 82, 655-666 (2000).
40. Newell CA, Birch-Machin I, Hibberd JM, Gray JC. Expression of green fluorescent protein from bacterial and plastid promoters in tobacco chloroplasts. Transgenic Res. 12(5), 631-634 (2003).
41. Knoblauch M, Hibberd JM, Gray JC, van Bel AJE. A galinstan expansion femtosyringe for microinjection of eukaryotic organelles and prokaryotes. Nat. Biotechnol. 17(9), 906-909 (1999).
42. Bock R. Transgenic plastids in basic research and plant biotechnology. J. Mol. Biol. 312(3), 425-438 (2001).
43. Golds T, Maliga P, Koop H-U. Stable plastid transformation in PEG-treated protoplasts of Nicotiana tabacum. Nat. Biotechnol. 11(1), 95-97 (1993).
44. O'Neill C, Horvath GV, Horvath E, Dix PJ, Medgyesy P. Chloroplast transformation in plants: polyethylene glycol (PEG) treatment of protoplasts is an alternative to biolistic delivery systems. Plant J. 3(5):729-738(1993)
45. Carrer H, Hockenberry TN, Svab Z, Maliga P. Kanamycin resistance as a selectable marker for plastid transformation in tobacco. Mol. Gen. Genet. 241(1-2), 49-56 (1993).
46. Huang FC, Klaus SMJ, Herz S, Zou Z, Koop HU, Golds TJ. Efficient plastid transformation in tobacco using the aphA-6 gene and kanamycin selection. Mol. Gen. Genomics 268(1), 19-27 (2002).
47. Kumar S, Dhingra A, Daniell H. Stable transformation of the cotton plastid genome and maternal inheritance of transgenes. Plant Mol. Biol. 56(2), 203-216 (2004).
48. Barone P, Zhang X-H, Widholm JM. Tobacco plastid transformation using the feedback-insensitive anthranilate synthase [a]-subunit of tobacco (ASA2) as a new selectable marker. J. Exp. Bot. 60(11), 3195-3202 (2009).
49. Bateman JM, Purton S. Tools for chloroplast transformation in Chlamydomonas: expression vectors and a new dominant selectable marker. Mol. Gen. Genet. 263(3), 404-410 (2000).
50. Goldschmidt-Clermont M. Transgenic expression of aminoglycoside adenine transferase in the chloroplast: a selectable marker for site-directed transformation of Chlamydomonas. Nucl. Acids Res. 19(15), 4083-4089 (1991).
51. Goldschmidt-Clermont M, Choquet Y, Girard-Bascou J, Michel F, Schirmer-Rahire M, Rochaix J-D. A small chloroplast RNA may be required for trans- splicing in Chlamydomonas reinhardtii. Cell 65(1), 135-143 (1991).
52. Newman SM, Boynton JE, Gillham NW, Randolph-Anderson BL, Johnson AM, Harris EH. Transformation of chloroplast ribosomal RNA genes in Chlamydomonas: molecular and genetic characterization of integration events. Genetics 126(4), 875-888 (1990).
53. Newman SM, Harris EH, Johnson AM, Boynton JE, Gillham NW. Nonrandom distribution of chloroplast recombination events in Chlamydomonas reinhardtii: evidence for a hotspot and an adjacent cold region. Genetics 132(2), 413-429 (1992).
54. Przibilla E, Heiss S, Johanningmeier U, Trebst A. Site-specific mutagenesis of the D1 subunit of photosystem II in wild-type Chlamydomonas. Plant Cell 3(2), 169-174 (1991).
55. Remacle C, Cline S, Boutaffala L et al. The ARG9 gene encodes the plastid-resident N-acetyl ornithine aminotransferase in the green alga Chlamydomonas reinhardtii. Eukaryot. Cell8(9), 1460-1463 (2009).
56. Kofer W, Eibl C, Steinmuller K, Koop H-U. PEG-mediated plastid transformation in higher plants. In Vitro Cell Dev. Biol. Plant. 34(4), 303-309 (1998).
57. Adam Z. Protein stability and degradation in plastids. Top. Curr. Genet. 19, 315-338 (2007).
58. Birch-Machin I, Newell CA, Hibberd JM, Gray JC. Accumulation of rotavirus VP6 protein in chloroplasts of transplastomic tobacco is limited by protein stability. Plant Biotechnol. J. 2(3), 261-270 (2004).
59. Scotti N, Alagna F, Ferraiolo E et al. High-level expression of the HIV-1 Pr55gag polyprotein in transgenic tobacco chloroplasts. Planta 229(5), 1109-1122 (2009).
60. Leelavathi S, Reddy VS. Chloroplast expression of His-tagged GUS-fusions: a general strategy to overproduce and purify foreign proteins using transplastomic plants as bioreactors. Mol. Breed 11(1), 49-58 (2003).
61. Lenzi P, Scotti N, Alagna F et al. Translational fusion of chloroplast-expressed human papillomavirus type 16 L1 capsid protein enhances antigen accumulation in transplastomic tobacco. Transgenic Res. 17(6), 1091-1102 (2008).
62. Molina A, Veramendi J. High stability of recombinant proteins expressed in tobacco chloroplasts. Open Biotechnol. J. 3, 67-72 (2009).
63. Oey M, Lohse M, Kreikemeyer B, Bock R. Exhaustion of the chloroplast protein synthesis capacity by massive expression of a highly stable protein antibiotic. Plant J. 57, 436-445 (2009).
64. Herz S, Fussl M, Steiger S, Koop H-U. Development of novel types of plastid transformation vectors and evaluation of factors controlling expression. Transgenic Res. 14(6), 969-982 (2005).
65. Koya V, Moayeri M, Leppla SH, Daniell H. Plant-based vaccine: mice immunized with chloroplast-derived anthrax protective antigen survive anthrax lethal toxin challenge. Infect. Immun. 73(12), 8266-8274 (2005).
66. Rigano MM, Manna C, Giulini A et al. Transgenic chloroplasts are efficient sites for high-yield production of the vaccinia virus envelope protein A27L in plant cells. Plant Biotechnol. J. 7(6), 577-591 (2009).
67. Sinagawa-Garcfa S, Tungsuchat-Huang T, Paredes-Lopez O, Maliga P. Next generation synthetic vectors for transformation of the plastid genome of higher plants. Plant Mol. Biol. 70(5), 487-498 (2009).
68. Giglione C, Meinnel T. Organellar peptide deformylases: universality of the N-terminal methionine cleavage mechanism. Trends Plant. Sci. 6(12), 566-572 (2001).
69. Giglione C, Vallon O, Meinnel T. Control of protein life-span by N-terminal methionine excision. EMBO J. 22(1), 13-23 (2003).
70. Fernandez-San Millan A, Farran I, Molina A, Mingo-Castel AM, Veramendi J. Expression of recombinant proteins lacking methionine as N-terminal amino acid in plastids: human serum albumin as a case study. J. Biotechnol. 127(4), 593-604 (2007).
71. Bally J, Paget E, Droux M, Job C, Job D, Dubald M. Both the stroma and thylakoid lumen of tobacco chloroplasts are competent for the formation of disulphide bonds in recombinant proteins. Plant Biotechnol. J. 6(1), 46-61 (2008).
72. Bock R. Plastid biotechnology: prospects for herbicide and insect resistance, metabolic engineering and molecular farming. Curr. Opin. Biotechnol. 18, 100-106 (2007).
73. Daniell H, Lee SB, Panchal T, Wiebe PO. Expression of the native cholera toxin B subunit gene and assembly as functional oligomers in transgenic tobacco chloroplasts. J. Mol. Biol. 311(5), 1001-1009 (2001).
74. Glenz K, Bouchon B, Stehle T, Wallich R, Simon MM, Warzecha H. Production of a recombinant bacterial lipoprotein in higher plant chloroplasts. Nat. Biotechnol. 24(1), 76-77 (2006).
75. Staub JM, Garcia B, Graves J et al. High-yield production of a human therapeutic protein in tobacco chloroplasts. Nat. Biotechnol. 18(3): 333-338(2000)
76. Tregoning JS, Nixon P, Kuroda H et al. Expression of tetanus toxin fragment C in tobacco chloroplasts. Nucleic Acids Res. 31, 1174-117 (2003)
77. Khan MS. Hybrid transcription-mediated transgene regulation in plastids. Trends Biotechnol. 24(11), 479-482 (2006).
78. Buhot L, Horvath E, Medgyesy P, Lerbs-Mache S. Hybrid transcription system for controlled plastid transgene expression. Plant J. 46(4), 700-707 (2006).
79. Tungsuchat T, Kuroda H, Narangajavana J, Maliga P. Gene activation in plastids by the CRE site-specific recombinase. Plant Mol. Biol. 61(4), 711-718 (2006).
80. Muhlbauer SK, Koop H-U. External control of transgene expression in tobacco plastids using the bacterial lac repressor. Plant J. 43(6), 941-946 (2005).
81. Kato K, Marui T, Kasai S, Shinmyo A. artificial control of transgene expression in Chlamydomonas reinhardtii chloroplast using the lac regulation system from Escherichia coli. J. Biosci. Bioeng. 104(3), 207-213 (2007).
82. Surzycki R, Cournac L, Peltier G, Rochaix J-D. Potential for hydrogen production with inducible chloroplast gene expression in Chlamydomonas. Proc. Natl Acad. Sci. USA 104(44), 17548-17553 (2007).
83. Grevich JJ, Daniell H. Chloroplast genetic engineering: recent advances and future perspectives. Crit. Rev. Plant Sci. 24(2), 83-107 (2005).
84. Ruf S, Karcher D, Bock R. Determining the transgene containment level provided by chloroplast transformation. Proc. Natl Acad. Sci. USA 104(17), 6998-7002 (2007).
85. Svab Z, Maliga P. Exceptional transmission of plastids and mitochondria from the transplastomic pollen parent and its impact on transgene containment. Proc. Natl Acad. Sci. USA 104(17), 7003-7008 (2007).
86. Haider N, Allainguillaume J, Wilkinson M. Spontaneous capture of oilseed rape (Brassica napus) chloroplasts by wild B. rapa: implications for the use of chloroplast transformation for biocontainment. Curr. Genet. 55(2), 139-150 (2009).
87. Murphy DJ. Improving containment strategies in biopharming. Plant Biotechnol. J. 5(5), 555-569 (2007).
88. Davoodi-Semiromi A, Schreiber M, Nalapalli S et al. Chloroplast-derived vaccine antigens confer dual immunity against cholera and malaria by oral or injectable delivery. Plant Biotechnol. J. 8(2), 223-242 (2010).
89. Tregoning JS, Clare S, Bowe F et al. Protection against tetanus toxin using a plant-based vaccine. Eur. J. Immunol. 35(4), 1320-1326 (2005).
90. Arlen PA, Singleton M, Adamovicz JJ, Ding Y, Davoodi-Semiromi A, Daniell H. Effective plague vaccination via oral delivery of plant cells expressing F1-V antigens in chloroplasts. Infect. Immun. 76(8), 3640-3650 (2008).
91. Bossi P, Garin D, Guihot A et al. Bioterrorism: management of major biological agents. Cell. Mol. Life Sci. 63(19-20), 2196-2212 (2006).
92. Watson J, Koya V, Leppla SH, Daniell H. Expression of Bacillus anthracis protective antigen in transgenic chloroplasts of tobacco, a non-food/feed crop. Vaccine 22(31-32), 4374-4384 (2004).
93. Rosales-Mendoza S, Alpuche-Solis AG, Soria-Guerra RE et al. Expression of an Escherichia coli antigenic fusion protein comprising the heat labile toxin B subunit and the heat stable toxin, and its assembly as a functional oligomer in transplastomic tobacco plants. Plant J. 57(1), 45-54 (2009).
94. Kang TJ, Loc NH, Jang MO et al. Expression of the B subunit of E. coli heat-labile enterotoxin in the chloroplasts of plants and its characterization. Transgenic Res. 12(6), 683-691 (2003).
95. Kang TJ, Han SC, Kim MY, Kim YS, Yang MS. Expression of non-toxic mutant of Escherichia coli heat-labile enterotoxin in tobacco chloroplasts. Protein Expr. Purif. 38(1), 123-128 (2004).
96. Soria-Guerra RE, Alpuche-Solis AG, Rosales-Mendoza S et al. Expression of a multi-epitope DPT fusion protein in transplastomic tobacco plants retains both antigenicity and immunogenicity of all three components of the functional oligomer. Planta 229(6), 1293-1302 (2009).
97. Hennig A, Bonfig K, Roitsch T, Warzecha H. Expression of the recombinant bacterial outer surface protein A in tobacco chloroplasts leads to thylakoid localization and loss of photosynthesis. FEBS J. 274(21), 5749-5758 (2007).
98. Dreesen IAJ, Hamri GC, Fussenegger M. Heat-stable oral alga-based vaccine protects mice from Staphylococcus aureus infection. J. Biotechnol. 145(3), 273-280 (2010).
99. Chung IS, Kim CH, Kim KI et al. Production of recombinant rotavirus VP6 from a suspension culture of transgenic tomato (Lycopersicon esculentum Mill.) cells. Biotechnol. Lett. 22(4), 251-255 (2000).
100. Kim CH, Kim KI, Hong SH, Lee YH, Chung IS. Improved production of recombinant rotavirus VP6 in sodium butyrate-supplemented suspension cultures of transgenic tomato (Lycopersicon esculentum Mill.) cells. Biotechnol. Lett. 23(13), 1061-1066 (2001).
101. Matsumura T, Itchoda N, Tsunemitsu H. Production of immunogenic VP6 protein of bovine group A rotavirus in transgenic potato plants. Arch. Virol. 147(6), 1263-1270 (2002).
102. Yu J, Langridge W. Expression of rotavirus capsid protein VP6 in transgenic potato and its oral immunogenicity in mice. Transgenic Res. 12(2), 163-169 (2003).
103. O'Brien GJ, Bryant CJ, Voogd C, Greenberg HB, Gardner RC, Bellamy AR. Rotavirus VP6 expressed by PVX vectors in Nicotiana benthamiana coats PVX rods and also assembles into viruslike particles. Virology 270(2), 444-453 (2000).
104. Zhang GG, Rodrigues L, Rovinski B, White KA. Production of HIV-1 p24 protein in transgenic tobacco plants. Mol. Biotechnol. 20(2), 131-136 (2002).
105. Buonaguro FM, Tornesello ML, Buonaguro L. Virus-like particle vaccines and adjuvants: the HPV paradigm. Expert Rev. Vaccines 8(10), 1379-1398 (2009).
106. Moscicki AB. HPV vaccines: today and in the future. J. Adolesc. Health 43(4 Suppl. 1), S26-S40 (2008).
107. Fernandez-San Millan A, Susana M, Hervas-Stubbs S et al. Human papillomavirus L1 protein expressed in tobacco chloroplasts self-assembles into virus-like particles that are highly immunogenic. Plant Biotechnol. J. 6(5), 427-441 (2008).
108. Warzecha H, Mason HS, Lane C et al. Oral immunogenicity of human papillomavirus-like particles expressed in potato. J. Virol. 77(16), 8702-8711 (2003).
109. Morgenfeld M, Eugenia Segretin M, Wirth S et al. Potato virus X coat protein fusion to human papillomavirus 16 E7 oncoprotein enhance antigen stability and accumulation in tobacco chloroplast. Mol. Biotechnol. 43(3), 243-249 (2009).
110. Massa S, Simeone P, Muller A, Benvenuto E, Venuti A, Franconi R. Antitumor activity of DNA vaccines based on the human papillomavirus-16 E7 protein genetically fused to a plant virus coat protein. Hum. Gene Ther. 19(4), 354-364 (2008).
111. Rigano MM, Manna C, Giulini A, Vitale A, Cardi T. Plants as biofactories for the production of subunit vaccines against bio-security-related bacteria and viruses. Vaccine 27(25-26), 3463-3466 (2009).
112. Molina A, Hervas-Stubbs S, Daniell H, Mingo-Castel AM, Veramendi J. High- yield expression of a viral peptide animal vaccine in transgenic tobacco chloroplasts. Plant Biotechnol. J. 2(2), 141-153 (2004).
113. Molina A, Veramendi J, Hervas-Stubbs S. Induction of neutralizing antibodies by a tobacco chloroplast-derived vaccine based on a B cell epitope from canine parvovirus. Virology 342(2), 266-275 (2005).
114. Ortigosa SM, Fernandez-San Millan A, Veramendi J. Stable production of peptide antigens in transgenic tobacco chloroplasts by fusion to the p53 tetramerisation domain. Transgenic Res. DOI: 10.1007/s11248-009-9348-y (2010) (Epub ahead of print).
115. Lentz EM, Segretin ME, Morgenfeld MM et al. High expression level of a foot and mouth disease virus epitope in tobacco transplastomic plants. Planta 231(2), 395 (2010).
116. Dus Santos MJ, Wigdorovitz A, Trono K et al. A novel methodology to develop a foot and mouth disease virus (FMDV) peptide-based vaccine in transgenic plants. Vaccine 20(7-8), 1141-1147 (2002).
117. Li Y, Sun M, Liu J, Yang Z, Zhang Z, Shen G. High expression of foot-and- mouth disease virus structural protein VP1 in tobacco chloroplasts. Plant Cell Rep. 25(4), 329-333 (2006).
118. Sun M, Qian K, Su N, Chang H, Liu J, Shen G. Foot-and-mouth disease virus VP1 protein fused with cholera toxin B subunit expressed in Chlamydomonas reinhardtii chloroplast. Biotechnol. Lett. 25(13), 1087-1092 (2003).
119. He DM, Qian KX, Shen GF et al. Recombination and expression of classical swine fever virus (CSFV) structural protein E2 gene in Chlamydomonas reinhardtii chroloplasts. Colloids Surf. B Biointerfaces 55(1), 26-30 (2007).
120. Shao HB, He DM, Qian KX, Shen GF, Su ZL. The expression of classical swine fever virus structural protein E2 gene in tobacco chloroplasts for applying chloroplasts as bioreactors. C. R. Biol. 331(3), 179-184 (2008).
121. Sim J-S, Pak H-K, Kim D-S, Lee S-B, Kim Y-H, Hahn B-S. Expression and characterization of synthetic heat-labile enterotoxin B subunit and hemagglutinin- neuraminidase-neutralizing epitope fusion protein in Escherichia coli and tobacco chloroplasts. Plant Mol. Biol. Rep. 27(3),399 (2009).
122. Zhou YX, Lee MY, Ng JM et al. A truncated hepatitis E virus ORF2 protein expressed in tobacco plastids is immunogenic in mice. World J. Gastroenterol. 12(2), 306-312 (2006).
123. Lee MY, Zhou Y, Lung RW et al. Expression of viral capsid protein antigen against Epstein-Barr virus in plastids of Nicotiana tabacum cv. SR1. Biotechnol. Bioeng. 94(6), 1129-1137 (2006).
124. Li HY, Ramalingam S, Chye ML. Accumulation of recombinant SARS-CoV spike protein in plant cytosol and chloroplasts indicate potential for development of plant-derived oral vaccines. Exp. Biol. Med. (Maywood) 231(8), 1346-1352 (2006).
125. Chebolu S, Daniell H. Stable expression of Gal/GalNAc lectin of Entamoeba histolytica in transgenic chloroplasts and immunogenicity in mice towards vaccine development for amoebiasis. Plant Biotechnol. J. 5(2), 230-239 (2007).
126. Langhorne J, Ndungu FM, Sponaas AM, Marsh K. Immunity to malaria: more questions than answers. Nat. Immunol. 9(7), 725-732 (2008).
127. Strobel S, Mowat AM. Immune responses to dietary antigens: oral tolerance. Immunol. Today 19(4), 173-181 (1998).
128. Ruhlman T, Ahangari R, Devine A, Samsam M, Daniell H. Expression of cholera toxin B-proinsulin fusion protein in lettuce and tobacco chloroplasts - oral administration protects against development of insulitis in non-obese diabetic mice. Plant Biotechnol. J. 5(4), 495-510 (2007).
129. Wang X, Brandsma M, Tremblay R et al. A novel expression platform for the production of diabetes-associated autoantigen human glutamic acid decarboxylase (hGAD65). BMC Biotechnol. 8, 87 (2008).
130. Ma S, Huang Y, Yin Z, Menassa R, Brandle JE, Jevnikar AM. Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4. Proc. Natl Acad. Sci. USA 101(15), 5680-5685 (2004).
131. Youm JW, Jeon JH, Kim H et al. High- level expression of a human (3-site APP cleaving enzyme in transgenic tobacco chloroplasts and its immunogenicity in mice. Transgenic Res. DOI: 10.1007/ s11248-010-9383-9388 (2010) (Epub ahead of print).
132. Farran I, McCarthy-Suarez I, Rio-Manterola F, Mansilla C, Lasarte JJ, Mingo-Castel AM. The vaccine adjuvant extra domain A from fibronectin retains its proinflammatory properties when expressed in tobacco chloroplasts. Planta 231(4), 977-990 (2010).
133. Lasarte JJ, Casares N, Gorraiz M et al. The extra domain A from fibronectin targets antigens to TLR4-expressing cells and induces cytotoxic T cell responses in vivo. J. Immunol. 178(2), 748-756 (2007).
134. Ye GN, Hajdukiewicz PT, Broyles D et al. Plastid-expressed 5-enolpyruvylshikimate- 3-phosphate synthase genes provide high level glyphosate tolerance in tobacco. Plant J. 25(3), 261-270 (2001).
135. Lelivelt C, McCabe M, Newell C et al. Stable plastid transformation in lettuce (Lactuca sativa L.). Plant Mol. Biol. 58(6), 763-774 (2005).
136. Tissot G, Canard H, Nada M, Martone A, Botterman J, Dubald M. Translocation of aprotinin, a therapeutic protease inhibitor, into the thylakoid lumen of genetically engineered tobacco chloroplasts. Plant Biotechnol. J. 6(3), 309-320 (2008).
137. Tremblay R, Wang D, Jevnikar AM, Schmidt M.A. Tobacco, a highly efficient green bioreactor for production of therapeutic proteins. Biotechnol. Adv. 28(2), 214-221 (2010).
138. Sparrow P, Irwin J, Dale P, Twyman R, Ma J. Pharma-Planta: road testing the developing regulatory guidelines for plant-made pharmaceuticals. Transgenic Res. 16(2), 147-161 (2007).
139. Sidorov VA, Kasten D, Pang S-Z, Hajdukiewicz PTJ, Staub JM, Nehra NS. Stable chloroplast transformation in potato: use of green fluorescent protein as a plastid marker. Plant J. 19(2), 209-216 (1999).
140. Sugiura C, Sugita M. Plastid transformation reveals that moss tRNAArg- CCG is not essential for plastid function. PlantJ. 40(2), 314-321 (2004).
141. Ma JK-C, Barros E, Bock R et al. Molecular farming for new drugs and vaccines. Embo Rep. 6, 593-599 (2005).
142. Ma JKC, Chikwamba R, Sparrow P, Fischer R, Mahoney R, Twyman RM. Plant-derived pharmaceuticals - the road forward. Trends Plant Sci. 10(12), 580-585 (2005).
143. Spok A, Twyman RM, Fischer R, Ma JKC, Sparrow PAC. Evolution of a regulatory framework for pharmaceuticals derived from genetically modified plants. Trends Biotechnol. 26(9), 506-517 (2008).
144. Giritch A, Marillonnet S, Engler C et al. Rapid high-yield expression of full-size IgG antibodies in plants coinfected with noncompeting viral vectors. Proc. Natl Acad. Sci. USA 103(40), 14701-14706 (2006).
145. Davarpanah S, Jung S, Kim Y et al. Stable plastid transformation in Nicotiana benthamiana. J. Plant Biology 52(3), 244-250 (2009).
146. Castilho A, Strasser R, Stadlmann J et al. In planta protein sialylation through over-expression of the respective mammalian pathway. J. Biol. Chem. 285(21), 15923-15930. (2010).
147. Maliga P, Svab Z. Engineering the plastid genome of Nicotiana sylvestris, a diploid model species for plastid genetics In: Plant Chromosome Engineering: Methods and Protocols. Birchler JJ (Ed.). Humana Press, Totowa, NJ, USA (2010)
148. Sourrouille C, Marquet-Blouin E, D'Aoust MA et al. Down-regulated expression of plant-specific glycoepitopes in alfalfa. Plant Biotechnol. J. 6(7), 702-721 (2008).
149. Floss D, Falkenburg D, Conrad U. Production of vaccines and therapeutic antibodies for veterinary applications in transgenic plants: an overview. Transgenic Res. 16(3), 315-332 (2007).
150. Santi L. Plant derived veterinary vaccines. Vet. Res. Commun. 33(0), 61-66 (2009).
151. Schiller JT, Nardelli-Haefliger D. Chapter 17: second generation HPV vaccines to prevent cervical cancer. Vaccine 24(Suppl. 3), S147-S153 (2006).
152. Stanley M, Gissmann L, Nardelli- Haefliger D. Immunobiology of human papillomavirus infection and vaccination - implications for second generation vaccines. Vaccine, 26(Suppl. 10), K62-K67 (2008).
153. Cox KM, Sterling JD, Regan JT et al. Glycan optimization of a human monoclonal antibody in the aquatic plant Lemna minor. Nat. Biotechnol. 24(12), 1591-1597 (2006).
154. Koprivova A, Stemmer C, Altmann F et al. Targeted knockouts of Physcomitrella lacking plant-specific immunogenic N-glycans. Plant Biotechnol. J. 2(6), 517-523 (2004).
155. Koop HU, Steinmuller K, Wagner H, Rossler C, Eibl C, Sacher L. Integration of foreign sequences into the tobacco plastome via polyethylene glycol-mediated protoplast transformation. Planta 199(2), 193-201 (1996).
156. Sikdar SR, Serino G, Chaudhuri S, Maliga P. Plastid transformation in Arabidopsis thaliana. Plant Cell. Rep. 18(1), 20-24 (1998).
157. Khan MS, Maliga P. Fluorescent antibiotic resistance marker for tracking plastid transformation in higher plants. Nat. Biotechnol. 17(9), 910-915 (1999).
158. Ruf S, Hermann M, Berger IJ, Carrer H, Bock R. Stable genetic transformation of tomato plastids and expression of a foreign protein in fruit. Nat. Biotechnol. 19, 870-875 (2001).
159. Daniell H, Muthukumar B, Lee SB. Marker free transgenic plants: engineering the chloroplast genome without the use of antibiotic selection. Curr. Genet. 39, 109-116 (2001).
160. Skarjinskaia M, Svab Z, Maliga P. Plastid transformation in Lesquerella fendleri, an oilseed Brassicacea. Transgenic Res. 12(1), 115-122 (2003).
161. Hou B-K, Zhou Y-H, Wan L-H et al. Chloroplast transformation in oilseed rape. Transgenic Res. 12(1), 111-114 (2003).
162. Kumar S, Dhingra A, Daniell H. Plastid-expressed betaine aldehyde dehydrogenase gene in carrot cultured cells, roots, and leaves confers enhanced salt tolerance. Plant Physiol. 136(1), 2843-2854 (2004).
163. Zubko MK, Zubko EI, van Zuilen K, Meyer P, Day A. Stable transformation of petunia plastids. Transgenic Res. 13(6), 523-530 (2004).
164. Dufourmantel N, Pelissier B, Garcon F, Peltier G, Ferullo J-M, Tissot G. Generation of fertile transplastomic soybean. Plant Mol. Biol. 55(4), 479-489.
165. Matveena NA, Shakhoviskii AM, Kuchuk NV. Stable transformation of Solanum rickii chloroplast DNA. Tsitol. Genet. 39(5), 3-8 (2005).
166. Nugent GD, ten Have M, van der Gulik A, Dix PJ, Uijtewaal BA, Mordhorst AP. Plastid transformants of tomato selected using mutations affecting ribosome structure. Plant Cell. Rep. 24(6), 341-349
167. Kanamoto H, Yamashita A, Asao H et al. Efficient and stable transformation of Lactuca sativa L. cv. Cisco (lettuce) plastids. Transgenic Res. 15(2), 205-217
168. Okumura S, Sawada M, Park YW et al. Transformation of poplar (Populus alba) plastids and expression of foreign proteins in tree chloroplasts. Transgenic Res. 15(5), 637-646 (2006).
169. Nugent GD, Coyne S, Nguyen TT, Kavanagh TA, Dix PJ. Nuclear and plastid transformation of Brassica oleracea var. botrytis (cauliflower) using PEG- mediated uptake of DNA into protoplasts. Plant Sci. 170(1), 135-142 (2006).
170. Chiyoda S, Linley PJ, Yamato KT, Fukuzawa H, Yokota A, Kohchi T. Simple and efficient plastid transformation system for the liverwort Marchantia polymorpha L. suspension-culture cells. Transgenic Res. 16(1), 41-49 (2006).
171. Liu C-W, Lin C-C, Chen J, Tseng M-J. Stable chloroplast transformation in cabbage (Brassica oleracea L. var. capitata L.) by particle bombardment. Plant Cell Rep. 26, 1733-1744 (2007).
172. De Marchis F, Wang Y, Stevanato P, Arcioni S, Bellucci M. Genetic transformation of the sugar beet plastome. Transgenic Res. 18(1), 17-30 (2009).
173. Singh A, Verma S, Bansal K. Plastid transformation in eggplant (Solanum melongena L.). Transgenic Res. 19(1), 113-119 (2010).
174. Cheng L, Li HP, Qu B et al. Chloroplast transformation of rapeseed (Brassica napus) by particle bombardment of cotyledons. Plant Cell Rep. 29(4), 371-381 (2010).
175. Cox K, Peele CG. Chloroplasttransformation of duckweed. Biolex, Inc., NC, USA. WIPO patent WO/2005/005643 (2005).
176. Potato-based vaccine success comes too late www.newscientist.com/article/ dn7006-potatobased-vaccine-success-comes-too- late.html