Abstract
Peptides have unique properties that make them useful drug candidates for diverse indications, including allergy, infectious disease and cancer. Some peptides are intrinsically bioactive, while others can be used to induce precise immune responses by defining a minimal immunogenic region. The limitations of peptides, such as metabolic instability, short half-life and low immunogenicity, can be addressed by strategies such as multimerization or fusion to carriers, to improve their pharmacological properties. The remaining major drawback is the cost of production using conventional chemical synthesis, which is also difficult to scale-up. Over the last 15 years, plants have been shown to produce bioactive and immunogenic peptides economically and with the potential for large-scale synthesis. The production of peptides in plants is usually achieved by the genetic fusion of the corresponding nucleotide sequence to that of a carrier protein, followed by stable nuclear or plastid transformation or transient expression using bacterial or viral vectors. Chimeric plant viruses or virus-like particles can also be used to display peptide antigens, allowing the production of polyvalent vaccine candidates. Here we review progress in the field of plant-derived peptides over the last 5 years, addressing new challenges for diverse pathologies.
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Andrianova EP, Krementsugskaia SR, Lugovskaia NN, Mayorova TK, Borisov VV, Eldarov MA, Ravin NV, Folimonov AS, Skryabin KG (2011) Foot and mouth disease virus polyepitope protein produced in bacteria and plants induces protective immunity in guinea pigs. Biochemistry (Mosc) 76:339–346
Arazi T, Slutsky SG, Shiboleth YM, Wang Y, Rubinstein M, Barak S, Yang J, Gal-On A (2001) Engineering zucchini yellow mosaic potyvirus as a non-pathogenic vector for expression of heterologous proteins in cucurbits. J Biotechnol 87:67–82
Bandurska K, Brodzik R, Spitsin S, Kohl T, Portocarrero C, Smirnov Y, Pogrebnyak N, Sirko A, Koprowski H, Golovkin M (2008) Plant-produced hepatitis B core protein chimera carrying anthrax protective antigen domain-4. Hybridoma (Larchmt) 27:241–247
Basaran P, Rodriguez-Cerezo E (2008) Plant molecular farming: opportunities and challenges. Crit Rev Biotechnol 28:153–172
Black RE, Cousens S, Johnson HL, Lawn JE, Rudan I, Bassani DG, Jha P, Campbell H, Walker CF, Cibulskis R, Eisele T, Liu L, Mathers C (2010) Global, regional and national causes of child mortality in 2008: a systematic analysis. Lancet 375:1969–1987
Boivin EB, Lepage E, Matton DP, De Crescenzo G, Jolicoeur M (2010) Transient expression of antibodies in suspension plant cell suspension cultures is enhanced when co-transformed with the tomato bushy stunt virus p19 viral suppressor of gene silencing. Biotechnol Prog 26:1534–1543
Bolhassani A, Safaiyan S, Rafati S (2011) Improvement of different vaccine delivery systems for cancer therapy. Mol Cancer 10:3
Branco MC, Sigano DM, Schneider JP (2011) Materials from peptide assembly: towards the treatment of cancer and transmittable disease. Curr Opin Chem Biol 15:427–434
Bray BL (2003) Large-scale manufacture of peptide therapeutics. Nat Rev Drug 2:587–593
Breckpot K, Escors D (2009) Dendritic cells for active anti-cancer immunotherapy: targeting activation pathways through genetic modification. Endocr Metab Immune Disord Drug Targets 9:328–343
Burnet FM (1970) The concept of immunological surveillance. Prog Exp Tumor Res 13:1–27
Campbell JD, Buckland KF, McMillan SJ, Kearley J, Oldfield WL, Stern LJ, Gronlund H, van Hage M, Reynolds CJ, Boyton RJ, Cobbold SP, Kay AB, Altmann DM, Lloyd CM, Larche M (2009) Peptide immunotherapy in allergic asthma generates IL-10-dependent immunological tolerance associated with linked epitope suppression. J Exp Med 206:1535–1547
Castilho A, Strasser R, Stadlmann J, Grass J, Jez J, Gattinger P, Kunert R, Quendler H, Pabst M, Leonard R, Altmann F, Steinkellner H (2010) In planta protein sialylation through overexpression of the respective mammalian pathway. J Biol Chem 285:15923–15930
Chua BY, Zeng WG, Lau YF, Jackson DC (2007) Comparison of lipopeptide-based immunocontraceptive vaccines containing different lipid groups. Vaccine 25:92–101
Circelli P, Donini M, Villani ME, Benvenuto E, Marusic C (2010) Efficient Agrobacterium-based transient expression system for the production of biopharmaceuticals in plants. Bioeng Bugs 1:221–224
Craik DJ, Simonsen S, Daly NL (2002) Thecyclotides: novel macrocyclic peptides as scaffolds in drug design. Curr Opin Discov Dev 5:251–260
Croft NP, Purcell AW (2011) Peptidomimetics: modifying peptides in the pursuit of better vaccines. Expert Rev Vaccines 10:211–226
Crotty S, Felgner P, Davies H, Glidewell J, Villareal L, Ahmed R (2003) Cutting edge: long-term B cell memory in humans after smallpox vaccination. J Immunol 171:4969–4973
Dalsgaard K, Uttenthal A, Jones TD, Xu F, Merryweather A, Hamilton WD, Langeveld JP, Boshuizen RS, Kamstrup S, Lomonossoff GP, Porta C, Vela C, Casal JI, Meloen RH, Rodgers PB (1997) Plant-derived vaccine protects target animals against a viral disease. Nat Biotechnol 15:248–252
Daniell H, Singh ND, Mason H, Streatfield SJ (2009) Plant-made vaccine antigens and biopharmaceuticals. Trends Plant Sci 14:669–679
Davidson MH (2011) Cardiovascular effects of glucagonlike peptide-1 agonist. Am J Cardiol 108:33–41
Ducat E, Deprez J, Gillet A, Noel A, Evrard B, Peulen O, Piel G (2011) Nuclear delivery of a therapeutic peptide by long circulating pH-sensitive liposomes: benefits over classical vesicles. Int J Pharm 25 (Epub ahead of print). doi:10.1016/j.ijpharm.2011.08.034
Durham SR, Walker SM, Varga EM, Jacobson MR, O’Brien F, Noble W (1999) Long-term clinical efficacy of grass-pollen immunotherapy. N Engl J Med 341:468–475
Ebner C, Siemann U, Bohle B, Willheim M, Wiedermann U, Schenk S, Klotz F, Ebner H, Kraft D, Scheiner O (1997) Immunological changes during specific immunotherapy of grass pollen allergy: reduced lymphoproliferative responses to allergen and shift from TH2 to TH1 in T-cell clones specific for Phl p 1, a major grass pollen allergen. Clin Exp Allergy 27:1007–1015
Edimayr J, Niespodziana K, Focke-Tejkl Linhart B, Valenta R (2011) Allergen-specific immunotherapy: towards combination vaccines for allergic and infectious diseases. Curr Top Microbiol Immunol 820:121–140
Elgaard L, Helenius A (2003) Quality control in the endoplasmic reticulum. Natl Rev Mol Cell Biol 4:181–191
Fellrath JM, Kettner A, Dufour N, Frigerio C, Schneeberger D, Leimgruber A, Corradin G, Spertini F (2003) Allergen-specific T-cell tolerance induction with allergen-derived long synthetic peptides: results of a phase I trial. J Allergy Clin Immunol 111:854–861
Fischer R, Schillberg S, Hellwig S, Twyman RM, Drossard J (2011) GMP issues for plant-derived recombinant proteins. Biotechnol Adv. doi: 10.1016/j.biotechadv.2011.08.007
Frolova OY, Petrunia IV, Komarova TV, Kosorukov VS, Sheval EV, Gleba YY, Dorokhov YL (2010) Trastuzumab-binding peptide display by Tobacco mosaic virus. Virology 407:7–13
Giuliani A, Rinaldi AC (2011) Beyond natural antimicrobial peptides: multimeric peptides and other peptidomimetic approaches. Cell Mol Life Sci 68:2255–2266
Gomord V, Sourrouille C, Fitchette AC, Bardor M, Pagny S, Lerouge P, Faye L (2004) Production and glycosylation of plant-made pharmaceuticals: the antibodies as a challenge. Plant Biotechnol J 2:83–100
Gomord V, Fitchette AC, Menu-Bouaouiche L, Saint-Jore-Dupas C, Plasson C, Michaud D, Faye L (2010) Plant-specific glycosylation patterns in the context of therapeutic protein production. Plant Biotechnol J 8:564–587
Gupta RK, Rost BE, Relyveld E, Siber GR (1995) Adjuvant properties of aluminium and calcium compounds. In: Powell MF, Newman MJ (eds) Vaccine design: the subunit and adjuvant approach. Plenum Press, New York, pp 229–248
Hashizume F, Hino S, Kakehashi M, Okajima T, Nadano D, Aoki N, Matsuda T (2008) Development and evaluation of transgenic rice seeds accumulating a type II-collagen tolerogenic peptide. Transgenic Res 17:1117–1129
Hoft DF, Brusic V, Sakala IG (2011) Optimizing vaccine development. Cell Microbiol 13:934–942
Huy NX, Yang MS, Kim TG (2011) Expression of a cholera toxin B subunit-neutralizing epitope of the porcine epidemic diarrhea virus fusion gene in transgenic lettuce (Lactuca sativa L.). Mol Biotechnol 48:201–209
Jegerlehner A, Tissot A, Lechner F, Sebbel P, Erdmann I, Kundig T, Bachi T, Storni T, Jennings G, Pumpens P, Renner WA, Bachmann MF (2002) A molecular assembly system that renders antigens of choice highly repetitive for induction of protective B cell responses. Vaccine 20:3104–3112
Jones SM, Pons L, Roberts JL, Scurlock AM, Perry TT, Kulis M, Shreffler WG, Steele P, Henry KA, Adair M, Francis JM, Durham S, Vickery BP, Zhong X, Burks AW (2009) Clinical efficacy and immune regulation with peanut oral immunotherapy. J Allergy Clin Immunol 124:292–300
Jutel M, Pichler WJ, Skrbic D, Urwyler A, Dahinden C, Muller UR (1995) Bee venom immunotherapy results in decrease of IL-4 and IL-5 and increase of IFN-gamma secretion in specific allergen-stimulated T cell cultures. J Immunol 154:4187–4194
Komarova TV, Baschieri S, Donini M, Marusic C, Benvenuto E, Dorokhov YL (2010) Transient expression systems for plant-derived bipharmaceuticals. Expert Rev Vaccines 9:859–876
Lai H and Chen Q (2011) Bioprocessing of plant-derived virus-like particles of Norwalk virus capsid protein under current Good Manufacture Practice regulations. Plant Cell Rep. doi:10.1007/s00299-011-1196-6
Larché M (2007) Peptide immunotherapy for allergic diseases. Allergy 62:325–331
Larman HB, Zhao Z, Laserson U, Li MZ, Ciccia A, Gakidis MA, Church GM, Kesari S, Leproust EM, Solimini NL, Elledge SJ (2011) Autoantigen discovery with a synthetic human peptidome. Nat Biotechnol 29:535–541
Lee SB, Li B, Jin S, Daniell H (2011) Expression and characterization of antimicrobial peptides Retrocyclin-101 and Protegrin-1 in chloroplasts to control viral and bacterial infections. Plant Biotechnol J 9:100–115
Lentz EM, Segretin ME, Morgenfeld MM, Wirth SA, Dus Santos MJ, Mozgovoj MV, Wigdorovitz A, Bravo-Almonacid FF (2010) High expression level of a foot and mouth disease virus epitope in tobacco transplastomic plants. Planta 231:387–395
Levine MM (2010) Immunogenicity and efficacy of oral vaccines in developing countries: lessons from a live cholera vaccine. BMC Biol 8:129
Lico C, Capuano F, Renzone G, Donini M, Marusic C, Scaloni A, Benvenuto E, Baschieri S (2006) Peptide display on Potato virus X: molecular features of the coat protein-fused peptide affecting cell-to-cell and phloem movement of chimeric virus particles. J Gen Virol 87:3103–3112
Lico C, Chen Q, Santi L (2008) Viral vectors for production of recombinant proteins in plants. J Cell Physiol 216:366–377
Lico C, Mancini C, Italiani P, Betti C, Boraschi D, Benvenuto E, Baschieri S (2009) Plant-produced potato virus X chimeric particles displaying an influenza virus-derived peptide activate specific CD8+ T cells in mice. Vaccine 27:5069–5076
Lien S, Lowman HB (2003) Therapeutic peptides. Trends Biotechnol 21:556–562
Liénard D, Sourrouille C, Gomord V, Faye L (2007) Pharming and transgenic plants. Biotechnol Annu Rev 13:115–147
Magis D, Schoenen J (2011) Treatment of migraine: update on new therapies. Curr Opin Neurol 24:203–210
Marillonnet S, Giritch A, Gils M, Kandzia R, Klimyuc V, Gleba Y (2004) In planta engineering of viral RNA replicons: efficient assembly by recombination of DNA modules delivered by Agrobacterium. Proc Natl Acad Sci USA 101:6852–6857
Masuta C, Yamana T, Tacahashi Y, Uyeda I, Sato M, Ueda S, Matsumura T (2000) Development of clover yellow vein virus as an efficient, stable gene-expression system for legume species. Plant J 23:539–546
Matoba N, Kajiura H, Cherni I, Doran JD, Bomsel M, Fujiyama K, Mor TS (2009) Biochemical and immunological characterization of the plant-derived candidate human immunodeficiency virus type 1 mucosal vaccine CTB-MPR. Plant Biotechnol J 7:129–145
Meshcheryakova YA, Eldarov MA, Migunov AI, Stepanova LA, Repko IA, Kiselev CI, Lomonossoff GP, Skryabin KG (2009) Cowpea mosaic virus chimeric particles bearing the ectodomain of matrix protein 2 (M2E) of the influenza A virus: production and characterization. Appl Mol Biol 43:685–694
Möbs C, Slotosch C, Löffler H, Jakob T, Hertl M, Pfützner W (2010) Birch pollen immunotherapy leads to differential induction of regulatory T cells and delayed helper T cell immune deviation. J Immunol 184:2194–2203
Moldaver D, Larché M (2011) Immunotherapy with peptides. Allergy 66:784–791
Mosekilde L, Torring O, Rejnmark L (2011) Emerging anabolic treatments in osteoporosis. Curr Drug Saf 6:62–74
Moyle PM, Toth I (2008) Self-adjuvanting lipopeptide vaccines. Curr Med Chem 15:506–516
Mukherjee P, Tinder TL, Basu GD, Pathangey LB, Chen L, Gendler SJ (2004) Therapeutic efficacy of MUC1-specific cytotoxic T lymphocytes and CD137 co-stimulation in a spontaneous breast cancer model. Breast Dis 20:53–63
Muntz K (1998) Deposition of storage proteins. Plant Moll Biol 38:77–99
Natilla A, Nemchinov LG (2008) Improvement of PVX/CMV CP expression tool for display of short foreign antigens. Protein Expr Purif 59:117–121
Nishida H, Sato T, Ogura T, Nakaya H (2009) New aspects for the treatment of cardiac diseases based on the diversity of functional controls on cardiac muscles: mitochondrial ion channels and cardioprotection. J Pharmacol Sci 109:341–347
Nouri-Aria KT, Wachholz PA, Francis JN, Jacobson MR, Walker SM, Wilcock LK, Staple SQ, Aalberse RC, Till SJ, Durham SR (2004) Grass pollen immunotherapy induces mucosal and peripheral IL-10 responses and blocking IgG activity. J Immunol 172:3252–3259
Nuzzaci M, Piazzolla G, Vitti A, Lapelosa M, Tortorella C, Stella I, Natilla A, Antonaci S, Piazzolla P (2007) Cucumber mosaic virus as a presentation system for a double hepatitis C virus-derived epitope. Arch Virol 152:915–928
Nuzzaci M, Bochicchio I, De Stradis A, Vitti A, Natilla A, Piazzolla P, Tamburro AM (2009) Structural and biological properties of Cucumber mosaic virus particles carrying hepatitis C virus-derived epitopes. J Virol Methods 155:118–121
Nuzzaci M, Vitti A, Condelli V, Lanorte MT, Tortorella C, Boscia D, Piazzolla P, Piazzolla G (2010) In vitro stability of Cucumber mosaic virus nanoparticles carrying a Hepatitis C virus-derived epitope under simulated gastrointestinal conditions and in vivo efficacy of an edible vaccine. J Virol Methods 165:211–215
Nykiforuk CL, Boothe JG, Murray EW, Keon RG, Goren HJ, Markley NA, Moloney MM (2006) Transgenic expression and recovery of biologically active recombinant human insulin from Arabidopsis thaliana seeds. Plant Biotechnol J 4:77–85
Obembe OO, Popoola JO, Leelavathi S, Reddy SV (2011) Advances in plant molecular farming. Biotechnol Adv 29:210–222
Ortigosa SM, Fernandez-San Millan A, Veramendi J (2010) Stable production of peptide antigens in transgenic tobacco chloroplasts by fusion to the p53 tetramerisation domain. Transgenic Res 19:703–709
Oude Munnink TH, Nagengast WB, Brouwers AH, Schroder CP, Hospers GA, Lub-de Hooge MN, van der Wall E, van Diest PJ, de Vries EG (2009) Molecular imaging of breast cancer. Breast 3:S66–S73
Pajno GB, Barberi S (2009) The history of sublingual immunotherapy. Int J Immunopathol Pharmacol 22:1–3
Paul M, Ma JK (2011) Plant-made pharmaceuticals: leading products and production platforms. Biotechnol Appl Biochem 58:58–67
Paz De la Rosa G, Monroy-Garcia A, Mora-Garcia Mde L, Pena CG, Hernandez-Montes J, Weiss-Steider B, Gomez-Lim MA (2009) An HPV 16 L1-based chimeric human papilloma virus-like particles containing a string of epitopes produced in plants is able to elicit humoral and cytotoxic T-cell activity in mice. Virol J 6:2
Phelps JP, Dang N, Rasochova L (2007) Inactivation and purification of cowpea mosaic virus-like particles displaying peptide antigens from Bacillus anthracis. J Virol Methods 141:146–153
Pinkhasov J, Alvarez ML, Rigano MM, Piensook K, Larios D, Pabst M, Grass J, Mukherjee P, Gendler SJ, Walmsley AM, Mason HS (2011) Recombinant plant-expressed tumour-associated MUC1 peptide is immunogenic and capable of breaking tolerance in MUC1.Tg mice. Plant Biotechnol J. doi:10.1111/j.1467-7652.2011.00614.x
Plotkin SA, Orenstein WA, Offit PA (2008) Vaccines, 5th edn. Saunders/Elsevier, Philadelphia
Pulendran B, Ahmed R (2011) Immunological mechanisms of vaccination. Nat Immunol 12:509–517
Purcell AW, McCluskey J, Rossjohn J (2007) More than one reason to rethink the use of peptides in vaccine design. Nat Rev Drug Discov 6:404–414
Qian B, Shen H, Liang W, Guo X, Zhang C, Wang Y, Li G, Wu A, Cao K, Zhang D (2008) Immunogenicity of recombinant hepatitis B virus surface antigen fused with preS1 epitopes expressed in rice seeds. Transgenic Res 17:621–631
Reddish M, MacLean GD, Koganty RR, Kan-Mitchell J, Jones V, Mitchell MS, Longenecker BM (1998) Anti-MUC1 class I restricted CTLs in metastatic breast cancer patients immunized with a synthetic MUC1 peptide. Int J Cancer 76:817–823
Reglodi D, Kiss P, Lubics A, Tamas A (2011) Review on the protective effects of PACAP in models of neurodegenerative diseases in vitro and in vivo. Curr Pharm Des 17:962–972
Robinson WH, Steinman L (2011) Human peptidome display. Nat Biotech 6:500–501
Rochlitz C, Figlin R, Squiban P, Salzberg M, Pless M, Herrmann R, Tartour E, Zhao Y, Bizouarne N, Baudin M, Acres B (2003) Phase I immunotherapy with a modified vaccinia virus (MVA) expressing human MUC1 as antigen-specific immunotherapy in patients with MUC1-positive advanced cancer. J Gene Med 5:690–699
Rybicki EP (2010) Plant-made vaccines for humans and animals. Plant Biotechnol J 8:620–637
Schähs M, Strasser R, Stadlmann J, Kunert R, Rademacher T, Steinkellner H (2007) Production of a monoclonal antibody in plants with a humanized N-glycosylation pattern. Plant Biotechnol J 5:657–663
Scholthof HB, Scholthof KB, Jackson AO (1996) Plant virus gene vectors for transient expression of foreign proteins in plants. Annu Rev Phytopathol 34:299–323
Sethi AA, Amar M, Shamburek RD, Remaley AT (2007) ApolipoproteinA-I mimetic peptides: possible new agents for the treatment of atherosclerosis. Curr Opin Investig Drugs 8:201–212
Sharma MK, Singh NK, Jani D, Sisodia R, Thungapathra M, Gautam JK, Meena LS, Singh Y, Ghosh A, Tyagi AK, Sharma AK (2008) Expression of toxin co-regulated pilus subunit A (TCPA) of Vibrio cholerae and its immunogenic epitopes fused to cholera toxin B subunit in transgenic tomato (Solanum lycopersicum). Plant Cell Rep 27:307–318
Sheen S (1983) Biomass and chemical composition of tobacco plants under high density growth. Beitr Tabakforsch Int 12:35–42
Shinmyo A, Kato K (2010) Molecular farming: production of drugs and vaccines in higher plants. J Antibiot 63:431–433
Skwarczynski M, Toth I (2011) Peptide-based subunit nanovaccines. Curr Drug Deliv 8:282–289
Soria-Guerra RE, Rosales-Mendoza S, Marquez-Mercado C, Lopez-Revilla R, Castillo-Collazo R, Alpuche-Solis AG (2007) Transgenic tomatoes express an antigenic polypeptide containing epitopes of the diphtheria, pertussis and tetanus exotoxins, encoded by a synthetic gene. Plant Cell Rep 26:961–968
Soria-Guerra RE, Rosales-Mendoza S, Moreno-Fierros L, Lopez-Revilla R, Alpuche-Solis AG (2011) Oral immunogenicity of tomato-derived sDPT polypeptide containing Corynebacterium diphtheriae, Bordetella pertussis and Clostridium tetani exotoxin epitopes. Plant Cell Rep 30:417–424
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
Stevenson CL (2009) Advances in peptide pharmaceuticals. Curr Pharm Biotechnol 10:122–137
Strasser R, Altmann F, Mach L, Glossl J, Steinkellner H (2004) Generation of Arabidopsis thaliana plants with complex N-glycans lacking β1, 2-linked xylose and core α1, 3-linked fucose. FEBS Lett 561:132–136
Strasser R, Stadlmann J, Schähs M, Stiegler G, Quendler H, Mach L, Glössl J, Weterings K, Pabst M, Steinkellner H (2008) Generation of glycoengineered Nicotiana benthamiana for the production of monoclonal antibodies with a homogeneous human-like N-glycan structure. Plant Biotechnol J 6:392–402
Strasser R, Castilho A, Stadlmann J, Kunert R, Quendler H, Gattinger P, Jez J, Rademacher T, Altmann F, Mach L, Steinkellner H (2009) Improved virus neutralization by plant-produced anti-HIV antibodies with a homogeneous β1, 4-galactosylated N-glycan profile. J Biol Chem 284:20479–20485
Suzuki K, Kaminuma O, Yang L, Takai T, Mori A, Umezu-Goto M, Ohtomo T, Ohmachi Y, Noda Y, Hirose S, Okumura K, Ogawa H, Takada K, Hirasawa M, Hiroi T, Takaiwa F (2011) Prevention of allergic asthma by vaccination with transgenic rice seed expressing mite allergen: induction of allergen-specific oral tolerance without bystander suppression. Plant Biotechnol J. doi:10.1111/j.1467-7652.2011.00613.x
Takagi H, Hiroi T, Yang L, Takamura K, Ishimitsu R, Kawauchi H, Takaiwa F (2008) Efficient induction of oral tolerance by fusing cholera toxin B subunit with allergen-specific T-cell epitopes accumulated in rice seed. Vaccine 26:6027–6030
Takagi H, Hiroi T, Hirose S, Yang L, Takaiwa F (2010) Rice seed ER-derived protein body as an efficient delivery vehicle for oral tolerogenic peptides. Peptides 31:1421–1425
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
Takaiwa F, Hirose S, Takagi H, Yang L, Wakasa Y (2009) Deposition of a recombinant peptide in ER-derived protein bodies by retention with cysteine-rich prolamins in transgenic rice seed. Planta 229:1147–1158
Tribbick G (2002) Multipin peptide libraries for antibody and receptor epitope screening and characterization. J Immunol Methods 267:27–35
Triguero A, Cabrera G, Cremata JA, Yuen CT, Wheeler J, Ramírez NI (2005) Plant-derived mouse IgG monoclonal antibody fused to KDEL endoplasmic reticulum-retention signal is N-glycosylated homogeneously throughout the plant with mostly high-mannose-type N glycans. Plant Biotechnol J 3:449–457
Van den Eynde BJ, van der Bruggen P (1997) T cell defined tumor antigens. Curr Opin Immunol 9:684–693
Vitti A, Piazzolla G, Condelli V, Nuzzaci M, Lanorte MT, Boscia D, De Stradis A, Antonaci S, Piazzolla P, Tortorella C (2010) Cucumber mosaic virus as the expression system for a potential vaccine against Alzheimer’s disease. J Virol Methods 169:332–340
Vlieghe P, Lisowski V, Martinez J, Khrestchatisky M (2010) Synthetic therapeutic peptides: science and market. Drug Discov Today 15:40–56
Wakasa Y, Tamakoshi C, Ohno T, Hirose S, Goto T, Nagaoka S, Takaiwa F (2011a) The hypocholesterolemic activity of transgenic rice seed accumulating lactostatin, a bioactive peptide derived from bovine milk beta-lactoglobulin. J Agric Food Chem 59:3845–3850
Wakasa Y, Zhao H, Hirose S, Yamauchi D, Yamada Y, Yang L, Ohinata K, Yoshikawa M, Takaiwa F (2011b) Antihypertensive activity of transgenic rice seed containing an 18-repeat novokinin peptide localized in the nucleolus of endosperm cells. Plant Biotechnol J 9:729–735
Webb AI, Dunstone MA, Williamson NA, Price JD, de Kauwe A, Chen W, Oakley A, Perlmutter P, McCluskey J, Aguilar MI, Rossjohn J, Purcell AW (2005) T cell determinants incorporating beta-amino acid residues are protease resistant and remain immunogenic in vivo. J Immunol 175:3810–3818
Wu D, Lee D, Sung YK (2011) Prospect of vasoactive intesstinal peptide therapy for COPD/PAH and asthma: a review. Respir Res 11:12–45
Yang CD, Liao JT, Lai CY, Jong MH, Liang CM, Lin YL, Lin NS, Hsu YH, Liang SM (2007) Induction of protective immunity in swine by recombinant bamboo mosaic virus expressing foot-and-mouth disease virus epitopes. BMC Biotechnol 7:62
Yusibov V, Mett V, Mett V, Davidson C, Muslychuk K, Gilliam S, Farese A, Macvittie T, Mann D (2005) Peptide-based candidate vaccine against respiratory syncytial virus. Vaccine 23:2261–2265
Zhang Y, Li J, Pu H, Jin J, Zhang X, Chen M, Wang B, Han C, Yu J, Li D (2010) Development of Tobacco necrosis virus A as a vector for efficient and stable expression of FMDV VP1 peptides. Plant Biotechnol J 8:506–523
Zhong W, Skwarczynski M, Toth I (2009) Lipid core peptide system for gene, drug and vaccine delivery. Aust J Chem 62:956–967
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This review was supported by the COST action ‘Molecular pharming: Plants as a Production Platform for High Value Proteins’ FA0804.
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Communicated by R. Reski.
A contribution to the Special Issue: Plant Molecular Pharming in 2012 and Beyond.
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Lico, C., Santi, L., Twyman, R.M. et al. The use of plants for the production of therapeutic human peptides. Plant Cell Rep 31, 439–451 (2012). https://doi.org/10.1007/s00299-011-1215-7
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DOI: https://doi.org/10.1007/s00299-011-1215-7