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Molecular pharming in cereal crops

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Abstract

There are many different agricultural expression systems that can be used for the large-scale production of recombinant proteins, but field-grown cereal crops are among the most attractive because recombinant proteins can be targeted to accumulate in the seed, and specifically in the endosperm, which has evolved naturally as a protein storage tissue. Within the developing endosperm, proteins are supplied with molecular chaperones and disulfide isomerases to facilitate folding and assembly, while the mature tissue is desiccated to prevent proteolytic degradation. Proteins expressed in cereal seeds can therefore remain stable for years in ambient conditions. Recent basic research has revealed a surprising diversity of protein targeting mechanisms in the endosperm, which can help to control post-translational modification and accumulation. Applied research and commercial development has seen several pharmaceutical proteins produced in cereals reach late stage preclinical development and the first clinical trials, with a number of companies now dedicated to developing cereal-based production platforms. In this review we discuss the basic science of molecular pharming in cereals, some of the lead product candidates, and challenges that remain to be addressed including the emerging regulatory framework for plant-made pharmaceuticals.

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Abbreviations

ER:

Endoplasmic reticulum

GRAS:

Generally regarded as safe

GM:

Genetically modified

PMP:

Plant made pharmaceutical

PMIP:

Plant made industrial protein

References

  • Al-Ahmad H, Galili S, Gressel J (2004) Tandem constructs to mitigate transgene persistence: tobacco as a model. Mol Ecol 13:697–710

    Article  PubMed  CAS  Google Scholar 

  • Aoyama T, Chua NH (1997) A glucocorticoid-mediated transcriptional induction system in transgenic plants. Plant J 11:605–612

    Article  PubMed  CAS  Google Scholar 

  • Arcalis E, Marcel S, Altmann F, Drakakaki G, Fischer R, Christou P, Stoger E (2004) Unexpected deposition patterns of recombinant proteins in post-ER compartments of wheat endosperm. Plant Physiol 136:3457–3466

    Article  PubMed  CAS  Google Scholar 

  • Azzoni AR, Takahashi K, Woodard SL, Miranda EA, Nikolov ZL (2005) Purification of recombinant aprotinin produced in transgenic corn seed: separation from CTI utilizing ion-exchange chromatography. Braz J Chem Eng 22:323–330

    Article  CAS  Google Scholar 

  • Baez J, Russell D, Craig J (2000) Corn seed production of therapeutic proteins moves forward: one company’s experience. Biopharm 13:50–54

    Google Scholar 

  • Bhattramakki D, Kriz AL (1996) Nucleotide sequence analysis of a novel globulin1 null allele from the Illinois high protein strain of maize. Plant Mol Biol 32:1215–1219

    Article  PubMed  CAS  Google Scholar 

  • Chikwamba RK, Scott MP, Mejia LB, Mason HS, Wang K (2003) Localization of a bacterial protein in starch granules of transgenic maize kernels. Proc Natl Acad Sci USA 100:11127–11132

    Article  PubMed  CAS  Google Scholar 

  • Christou P, Stoger E, Twyman RM (2004) Monocot systems for molecular farming. In: Fischer R, Schillberg S (eds) Molecular farming: plant-made pharmaceuticals and technical proteins. Wiley, NY, pp 55–67

    Google Scholar 

  • Claparols MI, Bassie L, Miro B, Del Duca S, Rodriguez J, Christou P, Serafini-Fracassini D, Capell T (2004) Transgenic rice as a vehicle for the production of the industrial enzyme transglutaminase. Transgenic Res 13:195–199

    Article  PubMed  CAS  Google Scholar 

  • Commandeur U, Twyman RM, Fischer R (2003) The biosafety of molecular pharming in plants. AgBiotechNet 5:110

    Google Scholar 

  • Daniell H, Streutfield SJ, Wycoff K (2001) Medical molecular pharming: production of antibodies, biopharmaceuticals and edible vaccines in plants. Trends Plant Sci 6:219–226

    Article  PubMed  CAS  Google Scholar 

  • Delaney DE (2002) Choice of crop species and development of transgenic product lines. In: Hood EE, Howard JA (eds) Plants as factories for protein production. Kluwer Academic Publishers, Dordrecht, pp 55–78

    Google Scholar 

  • Drakakaki G, Marcel S, Arcalis E, Altmann F, Gonzalez-Melendi P, Fischer R, Christou P, Stoger E (2006) The intracellular fate of a recombinant protein is tissue-dependent. Plant Physiol 141:578–586

    Article  PubMed  CAS  Google Scholar 

  • Dunwell J (2005) Technologies for biological containment of GM and non-GM crops. Defra Contract CPEC 47. http://www.defra.gov.uk/science/project_data/DocumentLibrary/CB02036/CB02036_3629_FRP.doc. Accessed 25 Oct 2007

  • Ellstrand NC, Prentice HC, Hancock JF (1999) Gene flow and introgression from domestic plants into their wild relatives. Annu Rev Ecol System 30:539–563

    Article  Google Scholar 

  • EMEA (2002) Points to consider on quality aspects of medicinal products containing active substances produced by stable transgene expression in higher plants (CPMP/BWP/764/02) [draft]. European Agency for the Evaluation of Medicinal Products, London, UK

    Google Scholar 

  • EMEA (2006) Guideline on the quality of biological active substances produced by stable transgene expression in higher plants. (EMEA/CHMP/BWP/48316/2006) [draft]. European Agency for the Evaluation of Medicinal Products, London, UK

    Google Scholar 

  • Farinas CS, Leite A, Miranda EA (2005) Aqueous extraction of maize endosperm: insights for recombinant protein hosts based on downstream processing. Process Biochem 40:3327–3336

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • FDA (2002) Guidance for industry. Drugs, biologics, and medical devices derived from bioengineered plants for use in humans and animals. Food and Drug Administration

  • Fischer R, Emans NJ, Twyman RM, Schillberg S (2003) Molecular farming of industrial proteins in plants. In: Fingerman M, Nagabhushanam R (eds) Recent advances in marine biotechnology, vol. 9 (biomaterials and bioprocessing). Science Publishers Inc., Enfield NH, pp 279–313

    Google Scholar 

  • Fischer R, Stoger E, Schillberg S, Christou P, Twyman RM (2004) Plant-based production of biopharmaceuticals. Curr Opin Plant Biol 7:152–158

    Article  PubMed  CAS  Google Scholar 

  • Giddings G, Allison G, Brooks D, Carter A (2000) Transgenic plants as factories for biopharmaceuticals. Nat Biotechnol 18:1151–1155

    Article  PubMed  CAS  Google Scholar 

  • Goff SA, Ricke D, Lan TH, Presting G, Wang R, Dunn M, Glazebrook J, Sessions A, Oeller P, Varma H et al (2002) A draft sequence of the rice genome (Oryza sativa L. ssp. japonica). Science 296:92–100

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Gressel J (2002) Molecular biology of weed control. Taylor & Francis, London

    Google Scholar 

  • Guerrero-Andrade O, Loza-Rubio E, Olivera-Flores T, Fehervari-Bone T, Gomez-Lim MA (2006) Expression of the newcastle disease virus fusion protein in transgenic maize and immunological studies. Transgenic Res 15:455–463

    Article  PubMed  CAS  Google Scholar 

  • Hellwig S, Drossard J, Twyman RM, Fischer R (2004) Plant cell cultures for the production of recombinant proteins. Nat Biotechnol 22:1415–1422

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Hood EE, Witcher DR, Maddock S, Meyer T, Baszczynski C, Bailey M, Flynn P, Register J, Marshall L, Bond D, Kulisek E, Kusnadi A, Evangelista R, Nikolov Z, Wooge C, Mehigh RJ, Hernan R, Kappel WK, Ritland D, Li CP, Howard JA (1997) Commercial production of avidin from transgenic maize: characterization of transformant, production, processing, extraction and purification. Mol Breed 3:291–306

    Article  CAS  Google Scholar 

  • Hood EE, Kusnadi A, Nikolov Z, Howard J (1999) Molecular pharming of industrial proteins from transgenic maize. In: Shahidi F, Kolodziejczyk P, Whitaker JR, Munguia AL, Fuller G (eds) Chemicals via higher plant bioengineering. Kluwer/Plenum, NY, pp 127–148

    Google Scholar 

  • Hood EE, Bailey MR, Beifuss K, Magallanes-Lundback M, Horn ME, Callaway E, Drees C, Delaney DE, Clough R, Howard JA (2003) Criteria for high-level expression of a fungal laccase gene in transgenic maize. Plant Biotechnol J 1:129–140

    Article  PubMed  CAS  Google Scholar 

  • Hood EE (2004) Where, oh where has my protein gone? Trends Biotechnol 22:53–55

    Article  PubMed  CAS  Google Scholar 

  • Hood EE, Love R, Lane J, Bray J, Clough R, Pappu K, Drees C, Hood KR, Yoon S, Ahmad A, Howard JA (2007) Subcellular targeting is a key condition for high-level accumulation of cellulase protein in transgenic maize seed. Plant Biotechnol J 5(6):709–719

    Article  PubMed  CAS  Google Scholar 

  • Horvath H, Huang J, Wong O, Kohl E, Okita T, Kannangara CJ, von Wettstein D (2000) The production of recombinant proteins in transgenic barley grains. Proc Natl Acad Sci U S A 97:1914–1919

    Article  PubMed  CAS  Google Scholar 

  • Jones MD, Brooks JS (1950) Effectiveness of distance and border rows in preventing outcrossing in corn, Oklahoma. Agricultural Experimental Station Bulletin, T-38

  • Lamphear BJ, Streatfield SJ, Jilka JM, Brooks CA, Barker DK, Turner DD, Delaney DE, Garcia M, Wiggins B, Woodard SL, Hood EE, Tizard IR, Lawhorn B, Howard JA (2002) Delivery of subunit vaccines in maize seed. J Control Release 85:169–180

    Article  PubMed  CAS  Google Scholar 

  • Lamphear BJ, Jilka JM, Kesl L, Welter M, Howard JA, Streatfield SJ (2004) A corn-based delivery system for animal vaccines: an oral transmissible gastroenteritis virus vaccine boosts lactogenic immunity in swine. Vaccine 22:2420–2424

    Article  PubMed  CAS  Google Scholar 

  • Law RD, Russell DA, Thompson LC, Schroeder SC, Middle CM, Tremaine MT, Jury TP, Delannay X, Slater SC (2006) Biochemical limitations to high-level expression of humanized monoclonal antibodies in transgenic maize seed endosperm. Biochim Biophys Acta 1760:1434–1444

    PubMed  CAS  Google Scholar 

  • Lin M, Rose-John S, Grötzinger J, Conrad U, Scheller J (2006) The functional expression of a biologically active fragment of soluble gp130 as an ELP fusion protein in transgenic plants: purification via inverse-transition-cycling. Biochem J 398:577–583

    Article  PubMed  CAS  Google Scholar 

  • Ma JK-C, Hiatt A, Hein M, Vine ND, Wang F, Stabila P, van Dolleweerd C, Mostov K, Lehner T (1995) Generation and assembly of secretory antibodies in plants. Science 268:716–719

    Article  PubMed  CAS  Google Scholar 

  • Ma JK-C, Drake PMW, Christou P (2003) The production of recombinant pharmaceuticals in plants. Nat Rev Genet 4:794–805

    Article  PubMed  CAS  Google Scholar 

  • Ma JK-C, Barros E, Bock R, Christou P, Dale PJ, Dix PJ, Fischer R, Irwin J, Mahoney R, Pezzotti M, Schillberg S, Sparrow P, Stoger E, Twyman RM (2005a) Molecular farming for new drugs and vaccines. Current perspectives on the production of pharmaceuticals in transgenic plants. EMBO Rep 6:593–599

    Article  PubMed  CAS  Google Scholar 

  • Ma JK-C, Chikwamba R, Sparrow P, Fischer R, Mahoney R, Twyman RM (2005b) Plant-derived pharmaceuticals—the road forward. Trends Plant Sci 10:580–585

    Article  PubMed  CAS  Google Scholar 

  • Makinen K, Nuutila AM (2004) Barley seed as a production host for industrially important proteins. AgBiotechNet 6:1–8

    Google Scholar 

  • Mavituna AM (2005) Production of recombinant human serum albumin in transgenic plants and plant cells. Master of Science dissertation, Rheinisch-Westfälischen Technischen Hochschule, Aachen

  • Menkhaus TJ, Bai Y, Zhang C, Nikolov ZL, Glatz CE (2004) Considerations for the recovery of recombinant proteins from plants. Biotechnol Prog 20:1001–1014

    Article  PubMed  CAS  Google Scholar 

  • Murphy DJ (2007) Improving containment strategies in biopharming. Plant Biotechnol J 5:555–569

    Article  PubMed  CAS  Google Scholar 

  • Nandi S, Yalda D, Lu S, Nikolov Z, Misaki R, Fujiyama K, Huang N (2005) Process development and economic evaluation of recombinant human lactoferrin expressed in rice grain. Transgenic Res 14:237–249

    Article  PubMed  CAS  Google Scholar 

  • Nicholson L, Gonzalez-Melendi P, van Dolleweerd C, Tuck H, Perrin Y, Ma JK-C, Fischer R, Christou P, Stoger E (2005) A recombinant multimeric immunoglobulin expressed in rice shows assembly-dependent subcellular localization in endosperm cells. Plant Biotechnol J 3:115–127

    Article  PubMed  CAS  Google Scholar 

  • Nikolov ZL, Woodard SL (2004) Downstream processing of recombinant proteins from transgenic feedstock. Curr Opin Biotechnol 15:479–486

    Article  PubMed  CAS  Google Scholar 

  • Nochi T, Takagi H, Yuki Y, Yang L, Masumura T, Mejima M, Nakanishi U, Matsumura A, Uozumi A, Hiroi T, Morita S, Tanaka K, Takaiwa F, Kiyono H (2007) Rice-based mucosal vaccine as a global strategy for cold-chain- and needle-free vaccination. Proc Natl Acad Sci U S A 104:10986–10991

    Article  PubMed  CAS  Google Scholar 

  • Padidam M (2003) Chemically regulated gene expression in plants. Curr Opin Plant Biol 6:169–177

    Article  PubMed  CAS  Google Scholar 

  • Perrin Y, Vaquero C, Gerrard I, Sack M, Drossard J, Stöger E, Christou P, Fischer R (2000) Transgenic pea seeds as bioreactors for the production of a single-chain Fv fragment (scFV) antibody used in cancer diagnosis and therapy. Mol Breed 6:345–352

    Article  CAS  Google Scholar 

  • Philip R, Darnowski DW, Maughan PJ, Vodkin LO (2001) Processing and localization of bovine β-casein expressed in transgenic soybean seeds under control of a soybean lectin expression cassette. Plant Sci 16:323–335

    Article  Google Scholar 

  • Qian B, Shen H, Liang W, Guo X, Zhang C, Wang Y, Li G, Wu A, Cao K, Zhang D (2007) Immunogenicity of recombinant hepatitis B virus surface antigen fused with preS1 epitopes expressed in rice seeds. Transgenic Res. doi:10.1007/s11248-007-9135-6

    PubMed  Google Scholar 

  • Ramessar K, Rademacher T, Sack M, Stadlmann J, Platis D, Stiegler G, Labrou N, Altmann F, Ma J, Stöger E, Capell T, Christou P Cost-effective production of a vaginal protein microbicide to prevent HIV transmission. Proc Natl Acad Sci USA (in press)

  • Ritala A, Nuutila AM, Aikasalo R, Kauppinen V, Tammisola J (2002) Measuring gene flow in the cultivation of transgenic barley. Crop Sci 42:278–285

    Article  PubMed  CAS  Google Scholar 

  • Schillberg S, Emans N, Fischer R (2002) Antibody molecular pharming in plants and plant cells. Phytochem Rev 1:45–54

    Article  CAS  Google Scholar 

  • Schillberg S, Fischer R, Emans N (2003) Molecular pharming of antibodies in plants. Naturwissenschften 90:145–155

    CAS  Google Scholar 

  • Schunmann PHD, Coia G, Waterhouse PM (2002) Biopharming the SimpliREDTM HIV diagnostic reagent in barley, potato and tobacco. Mol Breed 9:113–121

    Article  Google Scholar 

  • Seon J-H, Szarka JS, Moloney MM (2002) A unique strategy for recovering recombinant proteins from molecular pharming: affinity capture on engineered oilbodies. J Plant Biotechnol 4:95–101

    Google Scholar 

  • Sparrow PAC, Irwin JA, Dale PJ, Twyman RM, Ma JKC (2007) Pharma-Planta: road testing the developing regulatory guidelines for plant-made pharmaceuticals. Transgenic Res 16:147–161

    Article  PubMed  CAS  Google Scholar 

  • Sriraman R, Bardor M, Sack M, Vaquero C, Faye L, Fischer R, Finnern R, Lerouge P (2004) Recombinant anti-hCG antibodies retained in the endoplasmic reticulum of transformed plants lack core-xylose and core-α(1,3)-fucose residues. Plant Biotechnol J 2:279–287

    Article  PubMed  CAS  Google Scholar 

  • Stoger E, Vaquero C, Torres E, Sack M, Nicholson L, Drossard J, Williams S, Keen D, Perrin Y, Christou P, Fischer R (2000) Cereal crops as viable production and storage systems for pharmaceutical scFv antibodies. Plant Mol Biol 42:583–590

    Article  PubMed  CAS  Google Scholar 

  • Stoger E, Parker M, Christou P, Casey R (2001) Pea legumin overexpressed in wheat endosperm assembles into an ordered paracrystalline matrix. Plant Physiol 125:1732–1742

    Article  PubMed  CAS  Google Scholar 

  • Stoger E, Sack M, Fischer R, Christou P (2002a) Plantibodies: applications, advantages and bottlenecks. Curr Opin Biotechnol 13:161–166

    Article  PubMed  CAS  Google Scholar 

  • Stoger E, Sack M, Perrin Y, Vaquero C, Torres E, Twyman RM, Christou P, Fischer R (2002b) Practical considerations for pharmaceutical antibody production in different crop systems. Mol Breed 9:149–158

    Article  CAS  Google Scholar 

  • Stoger E, Ma JK, Fischer R, Christou P (2005a) Sowing the seeds of success: pharmaceutical proteins from plants. Curr Opin Biotechnol 16:167–173

    Article  PubMed  CAS  Google Scholar 

  • Stoger E, Sack M, Nicholson L, Fischer R, Christou P (2005b) Recent progress in plantibody technology. J Curr Pharm Des 11:2439–2457

    Article  PubMed  CAS  Google Scholar 

  • Streatfield SJ (2005) Plant-based vaccines for animal health. Rev Sci Techn-Offic Int Epizoo 24:189–199

    CAS  Google Scholar 

  • Streatfield SJ (2007) Approaches to achieve high-level heterologous protein production in plants. Plant Biotechnol J 5:2–15

    Article  PubMed  CAS  Google Scholar 

  • Tada Y, Utsumi S, Takaiwa F (2003) Foreign gene products can be enhanced by introduction into storage protein mutants. Plant Biotechnol J 1:411–422

    Article  PubMed  CAS  Google Scholar 

  • Takagi H, Hiroi T, Yang L, Tada Y, Yuki Y, Takamura K, Ishimitsu R, Kawauchi H, Kiyono H, Takaiwa F (2005) A rice-based edible vaccine expressing multiple T cell epitopes induces oral tolerance for inhibition of Th2-mediated IgE responses. Proc Natl Acad Sci USA 102:17525–17530

    Article  PubMed  CAS  Google Scholar 

  • Takaiwa F, Takagi H, Hirose S, Wakasa Y (2007) Endosperm tissue is good production platform for artificial recombinant proteins in transgenic rice. Plant Biotechnol J 5:84–92

    Article  PubMed  CAS  Google Scholar 

  • Ting JT, Lee K, Ratnayake C, Platt KA, Balsamo RA, Huang AH (1996) Oleosin genes in maize kernels having diverse oil contents are constitutively expressed independent of oil contents. Size and shape of intracellular oil bodies are determined by the oleosins/oils ratio. Planta 199:158–165

    Article  PubMed  CAS  Google Scholar 

  • Torres E, Vaquero C, Nicholson L, Sack M, Stöger M, Drossard J, Christou P, Fischer R, Perrin Y (1999) Rice cell culture as an alternative production system for functional diagnostic and therapeutic antibodies. Transgenic Res 8:441–449

    Article  PubMed  CAS  Google Scholar 

  • Torres E, Gonzales-Melendi P, Stöger E, Shaw P, Twyman RM, Nicholson L, Vaquero C, Fischer R, Christou P, Perrin Y (2001) Native and artificial reticuloplasmins co-accumulate in distinct domains of the endoplasmic reticulum (ER) and in post-ER vesicles. Plant Physiol 127:1212–1223

    Article  PubMed  CAS  Google Scholar 

  • Twyman RH, Stoger E, Schillberg S, Christou P, Fischer R (2003) Molecular pharming in plants: host systems and expression technology. Trends Biotechnol 21:570–579

    Article  PubMed  CAS  Google Scholar 

  • Twyman RM, Schillberg S, Fischer R (2005) Transgenic plants in the biopharmaceutical market. Expert Opin Emerg Drugs 10:185–218

    Article  PubMed  CAS  Google Scholar 

  • Twyman RM, Schillberg S, Fischer R (2007) Molecular pharming antibodies in plants. In: Ranalli P (ed) Improvement of crop plants for industrial end uses. Springer, Berlin, pp 435–470

    Chapter  Google Scholar 

  • USDA—Animal and Plant Health Inspection Service (2003) Field testing and plants engineered to produce pharmaceutical and industrial compounds. Fed Regis 68(46), March 10

    Google Scholar 

  • Van Droogenbroeck B, Cao J, Stadlmann J, Altmann F, Colanesi S, Hillmer S, Robinson DG, Van Lerberge E, Terryn N, Van Montagu M, Liang M, Depicker A, De Jaeger G (2007) Aberrant localization and underglycosylation of highly accumulating single-chain Fv-Fc antibodies in transgenic Arabidopsis seeds. Proc Natl Acad Sci U S A 104:1430–1435

    Article  PubMed  CAS  Google Scholar 

  • Warzecha H, Mason HS (2003) Benefits and risks of antibody and vaccine production in transgenic plants. J Plant Physiol 160:755–764

    Article  PubMed  CAS  Google Scholar 

  • Watson SA (1987) In: Watson SA, Ramstad PT (eds) Corn: chemistry and technology. Am. Assoc. Cereal Chemists, St. Paul, MN, pp 53–82

  • Wolt JD, Wang K, Peterson RKD (2006) Assessing risk of unintended antigen occurrence in food: a case instance for maize-expressed LT-B. Hum Ecol Risk Assess 12:1–15

    Article  CAS  Google Scholar 

  • Woodard SL, Mayor JM, Bailey MR, Barker DK, Love RT, Lane JR, Delaney DE, McComas-Wagner JM, Mallubhotla HD, Hood EE, Gangott LJ, Tichy SE, Howard JA (2003) Maize-derived bovine trypsin: characterization of the first large-scale, commercial product from transgenic plants. Biotechnol Appl Biochem 38:123–130

    Article  PubMed  CAS  Google Scholar 

  • Wright KE, Prior F, Sardana R, Altosaar I, Dudani AK, Ganz PR, Tackaberry ES (2001) Sorting of glycoprotein B from human cytomegalovirus to protein storage vesicles in seeds of transgenic tobacco. Transgenic Res 10:177–181

    Article  PubMed  CAS  Google Scholar 

  • Wu J, Yu L, Li L, Hu J, Zhou J, Zhou X (2007) Oral immunization with transgenic rice seeds expressing VP2 protein of infectious bursal disease virus induces protective immune responses in chickens. Plant Biotechnol J 5:570–578

    Article  PubMed  CAS  Google Scholar 

  • Xue GP, Patel M, Johnson JS, Smyth DJ, Vickers CE (2003) Selectable marker-free transgenic barley producing a high level of cellulase (1,4-beta-glucanase) in developing grains. Plant Cell Rep 21:1088–1094

    Article  PubMed  CAS  Google Scholar 

  • Yamagata H, Tanaka K (1986) The site of synthesis and accumulation of rice storage proteins. Plant Cell Physiol 27:135–145

    CAS  Google Scholar 

  • Yang D, Guo F, Huang N, Watkins S (2003) Expression and localisation of human lysozyme in the endosperm of transgenic rice. Planta 216:597–603

    PubMed  CAS  Google Scholar 

  • Yang L, Suzuki K, Hirose S, Wakasa Y, Takaiwa F (2007) Development of transgenic rice seed accumulating a major Japanese cedar pollen allergen (Cry j 1) structurally disrupted for oral immunotherapy. Plant Biotechnol J 5:815–826

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Zhong GY, Peterson D, Delaney DE, Bailey M, Witcher DR, Register JC III, Bond D, Li C-P, Marshall L, Kulisek E, Ritland D, Meyer T, Hood EE, Howard JA (1999) Commercial production of aprotinin in transgenic maize seeds. Mol Breed 5:345–356

    Article  CAS  Google Scholar 

  • Zhu Z, Hughes KW, Huang L, Sun B, Liu C, Li Y (1994) Expression of human alfa-interferon cDNA in transgenic rice plants. Plant Cell Tiss Org Cul 36:197–204

    Article  CAS  Google Scholar 

  • Zuo J, Chua NH (2000) Chemical-inducible systems for regulated expression of plant genes. Curr Opin Biotechnol 11:146–151

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

European Union Framework 6 Programme—The Pharma-Planta Integrated Project. LSH-2002-1.2.5-2; Acciones Complementarias (MEC) BIO2005-24826-E; Generalitat de Catalunya 2005SGR118; the Ramon y Cajol Program of MEC, Spain. Center CONSOLIDER on Agrigenomics funded by the Spanish Ministry of Education and Science.

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  1. Department de Produccio Vegetal I Ciencia Forestal, Universitat de Lleida, Av. Alcalde Rovira Roure, 191, 25198, Lleida, Spain

    Koreen Ramessar, Teresa Capell & Paul Christou

  2. ICREA (Institucio Catalana de Recerca I Estudis Avancats), Universitat de Lleida, Lleida, Spain

    Paul Christou

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  1. Koreen Ramessar
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Correspondence to Paul Christou.

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Ramessar, K., Capell, T. & Christou, P. Molecular pharming in cereal crops. Phytochem Rev 7, 579–592 (2008). https://doi.org/10.1007/s11101-008-9087-3

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