Document Type : Review Article
Authors
1 Department of Horticulture, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran
2 Department of Plant Breeding, Faculty of Agriculture, Tarbiat Modares University, Tehran, Iran
Abstract
Molecular farming, or bio-pharming, has recently received much of attention for production of valuable recombinant proteins, with a few already being marketed. The use of whole plants for synthesis of pharmaceutical proteins offers various advantages in economy, scalability and safety over conventional production systems. GM plants are suitable for the inexpensive production of large amounts of functional, recombinant macromolecules, such as blood substitutes, vaccines, anti-cancer antibodies, plasma proteins, enzymes, cytokines and growth factors, and the expressed proteins, ranging from the smallest antigen-binding domains, to full-length, and even multi-meric proteins, are almost comparable to their mammalian counterparts. Delivery of a biopharmaceutical product by direct ingestion of the modified food crops removes the need for purification. Such biopharmaceuticals and edible vaccines can be stored and distributed as seeds, tubers, or fruits, making immunization programs in developing countries potentially cheaper and easier. It is anticipated that this technology has the potential to greatly benefit human health by making safe recombinant pharmaceuticals widely available. Here, we discuss facts, recent developments and perspectives of this field in detail.
Keywords
Acosta, O. and Chaparro, A. (2008). Genetically modified food crops and public health. Acta biol Colomb, 13(3): 3-26.
Ahmad, A., Pereira, E.O., Conley, A.J., Richman, A.S and Menassa, R. (2010). Green biofactories: recombinant protein production in plants. Recent Pat Biotechnol, 4(3):242-259.
Ahmad, A., Pereira, E.O., Conley, A.J., Richman, A.S and Menassa, R. (2010). Green biofactories: recombinant protein production in plants. Recent Pat Biotechnol, 4(3):242-259.
| Alderborn, | A., | Sundstrˆm, | J., | Soeria-Atmadja, | D., |
| Sandberg, M., Andersson, H.C and Hammerling, U. (2010). Genetically modified plants for non-food or non-feed |
|||||
| purposes: | Straightforward | screening | for | their |
appearance in food and feed. Food and Chemical Toxicology, 48: 453ñ464.
Baesi, M., Nabati-Ahmadi, D., Rajabi-Memari, H., Siahpoosh, M.R., Abdollahi, M.R and Jaberolansar, N. (2011). Cloning and transformation of hepatitis B surface antigen (HBsAg) gene to tomato (Lycopersiconesculentum
Mill.). Jundishapur J of Natural Pharmaceutical Products, 6(1): 32-41.
Bagheri, K.H. (2009). Gamma-Oleosin interferon gene transfer to canola and study of transgenic plants. Ph.D. thesis. Department of Plant Breeding, Faculty of Agriculture, Tarbiat Modarres University. Tehran - Iran.
Bansal, K.C. and Sharma, R.K. (2003). Chloroplast transformation as a tool for prevention of gene flow from GM crops to weedy or wild relatives. Curr Sci, 84(10): 1286-1287.
Bock, R. (2001). Transgenic plastids in basic research and plant biotechnology. J Mol Biol, 312: 425-438.
Bock, R. and Warzecha, H. (2010). Solar-powered factories for new vaccines and antibiotics. Trends Biotechnol, 28(5): 246-252.
Breyer, D., Goossens, M., Herman, Ph. and Sneyers, M. (2009). Biosafety considerations associated with molecular farming in genetically modified plants. J Med Plants Res, 3(11): 825-838.
Chebolu, S and Daniell, H. (2009). Chloroplast-derived vaccine antigens and biopharmaceuticals: expression, folding, assembly and functionality. Curr Top Microbiol Immunol, 332: 33-54.
Chen, M., Liu, X., Wang, Z., Song, J., Qi, Q and Wang, P.G. (2005). Modification of plant N-glycans processing: the future of producing therapeutic protein by transgenic plants. Med Res Rev, 25(3): 343-360.
Clarke, J.L. and Daniell, H. (2011). Plastid biotechnology for crop production: present status and future perspectives. Plant Mol Biol, 76: 211ñ220.
Daniell, H. (1999). Environmentally friendly approaches to genetic engineering. In Vitro Cell Dev Biol Plant, 35: 361ñ368.
Daniell, H., Chebolu, S., Kumar, Sh., Singleton, M. and Falconer, R. (2005). Chloroplast-derived vaccine antigens and other therapeutic proteins. Vaccine, 23(15): 1779-1783.
Daniell, H., Khan, M.S. and Allison, L. (2002). Milestones in chloroplast genetic engineering: an environmentally friendly era in biotechnology. Trends in Plant Science,7(2): 84-91.
Daniell, H., Streatfield, S.J and Wycoff, K. (2001). Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants. Trends Plant Sci, 6(5): 219-226.
Davoodi-Semiromi, A., Schreiber, M., Nalapalli, S., Verma, D., Singh, N.D., Banks, R.K., Chakrabarti, D and Daniell, H. (2010). Chloroplast-derived vaccine antigens confer dual immunity against cholera and malaria by oral or injectable delivery. Plant Biotechnol J, 8: 223ñ242.
Desai, P.N., Shrivastava, N and Padh, H. (2010). Production of heterologous proteins in plants: strategies for optimal expression. Biotechnol Adv, 28(4): 427-435.
Dymyad, S. (2007). VHH antibody gene transfer to canola and regeneration of transgenic plants. M.Sc. thesis. Department of Biotechnology, Faculty of Agriculture, Tarbiat Modarres University. Tehran - Iran.
Fischer, R and Emans, N. (2000). Molecular farming of pharmaceutical proteins. Transgenic Res, 9(4-5): 279-299.
Fischer, R., Drossard, J., Commandeur, U., Schillberg, S and Emans, N. (1999). Towards molecular farming in the future: moving from diagnostic protein and antibody production in microbes to plants. Biotechnol Appl
Biochem, 30(2): 101-108.
Fischer, R., Hoffmann, K., Schillberg, S and Emans, N. (2000). Antibody production by molecular farming in plants. J Biol Regul Homeost Agents, 14(2): 83-92.
Fischer, R., Schillberg, S., Hellwig, S., Twyman, R.M and Drossard, J. (2012). GMP issues for recombinant plantderived pharmaceutical proteins. Biotechnol Adv, 30(2): 434-439.
Flinn, J.E and Zavon, J.A. (2004). Green plants as biofactories for drugs. Biopharm Int, 17: 42ñ49.
Gao, M., Li, Y., Xue, X., Wang, X. and Long, J. (2012). Stable plastid transformation for high-level recombinant protein expression: promises and challenges. Journal of Biomedicine and Biotechnology, Vol 2012, Article ID
158232, 16 pages.
Gleba, Y., Klimyuk, V and Marillonnet, S. (2007). Viral vectors for the expression of proteins in plants. Curr Opin Biotechnol, 18: 134ñ141.
Gomord, V., Fitchette, A.C., Menu-Bouaouiche, L., SaintJore-Dupas, C., Plasson, C., Michaud, D and Faye, L. (2010). Plant-specific glycosylation patterns in the context of therapeutic protein production. Plant
Biotechnol J, 8(5): 564-587.
Hellwig, S., Drossard, J., Twyman, R.M and Fischer, R. (2004). Plant cell cultures for the production of recombinant proteins. Nat Biotechnol, 22(11): 1415- 1422.
Honari, H. (2008). Expression of PA gene from Bacillus antracis in Iranian lettuce (Lactuca sativa). Ph.D. thesis, Department of Plant Breeding, College of Agriculture, Tehran University. Tehran - Iran.
Ismaili, A., Jalali-Javaran, M., Rasaee, M.J., Rahbarizadeh, F and Rajabi-memari, H. (2006). Cloning and expression of recombinant camelid single-domain antibody in tobacco. Iranian Journal of Biotechnology, 4(3):162-168.
Kashani, K., Jalali Javaran, M., Mohebodini, M., Moieni, A and Sheikhi Deh Abadi M. (2012). Regeneration and Agrobacterium-mediated transformation of three potato cultivars (Solanum tuberosum cv. Desiree, Agria and
Marfona) by human proinsulin gene. AJCS 6(7): 1212- 1220.
Ko, K., Ahn, M.H., Song, M., Choo, Y.K., Kim, H.S., Ko, K and Joung, H. (2008). Glyco-engineering of biotherapeutic proteins in plants. Mol Cells, 25(4): 494-503.
Ko, K., Brodzik, R and Steplewski, Z. (2009). Production of antibodies in plants: approaches and perspectives. Curr Top Microbiol Immunol, 332: 55-78.
Krattiger, A. and Mahoney, R.T. (2007). Specific IP issues with molecular pharming: case study of plant-derived vaccines. In Intellectual Property Management in Health and Agricultural Innovation: A Handbook of Best Practices. Volume 2. 2nd edition. Edited by Krattiger, A. Mahoney,
R.T., Nelsen, L., Thomson, J.A., Bennett, A.B., Satyanarayana, K., Graff, G.D., Fernandez, C. and Kowalski, S.P. Oxford, UK: MIHR and Davis, USA: PIPRA. 1809-1817. (Available online at www.ipHandbook.org).
Larrick, J.W., Yu, L., Naftzger, C., Jaiswal, S and Wycoff, K. (2001). Production of secretory IgA antibodies in plants. Biomol Eng, 18(3): 87-94.
Lerouge, P., Bardor, M., Pagny, S., Gomord, V and Faye, L. (2000). N-glycosylation of recombinant pharmaceutical glycoproteins produced in transgenic plants: towards an humanisation of plant N-glycans. Curr Pharm Biotechnol, 1(4): 347-354.
Lugade, A.A., Kalathil, S., Heald, J.L and Thanavala, Y. (2010). Transgenic plant-based oral vaccines. Immunol Invest, 39(4-5): 468-482.
Maliga, P and Bock, R. (2011). Plastid biotechnology: food, fuel, and medicine for the 21st century. Plant Physiol, 155: 1501ñ1510.
Masoumi-Asl, A., Jalali-Javaran, M., Mahbodi, F and Alizadeh, H. (2010). Cloning and expression of tissue plasminogen activator (t-PA) gene in tobacco plants. Scientific Research and Essays, 5(9): 917-922.
Mohebodini, M., Jalali-Javaran, M., Mahboodi, F., Alizadeh, H and Ajhdari, H. (2009). Human proinsulin gene cloning in plant expression vector pCAMBIA1304. 6th National Biotechnology Congress of Iran, Tehran-Iran, 13-15 August 2009.
Naqvi, Sh., Ramessar, K., FarrÈ, G., Sabalza, M., Miralpeix, B., Twyman, R.M., Capell, T., Zhu, Ch. and Christou, P. (2011). High-value products from transgenic maize. Biotechnol Adv, 29: 40ñ53.
Pogue, G.P., Vojdani, F., Palmer, K.E., Hiatt, E., Hume, S., Phelps, J., Long, L., Bohorova, N., Kim, D., Pauly, M., Velasco, J., Whaley, K., Zeitlin, L., Garger, S.J., White, E., Bai, Y., Haydon, H and Bratcher, B. (2010). Production of
pharmaceutical-grade recombinant aprotinin and a monoclonal antibody product using plant-based transient expression systems. Plant Biotechnol J, 8(5):638-654.
Rahimifar, P. (2009). Human IFN gene transfer to canola. M.Sc. thesis. Department of Biotechnology, Aborayhan campus of Tehran University. Tehran - Iran.
Baesi, M., Nabati-Ahmadi, D., Rajabi-Memari, H., Siahpoosh, M.R., Abdollahi, M.R and Jaberolansar, N. (2011). Cloning and transformation of hepatitis B surface antigen (HBsAg) gene to tomato (Lycopersiconesculentum
Mill.). Jundishapur J of Natural Pharmaceutical Products, 6(1): 32-41.
Bagheri, K.H. (2009). Gamma-Oleosin interferon gene transfer to canola and study of transgenic plants. Ph.D. thesis. Department of Plant Breeding, Faculty of Agriculture, Tarbiat Modarres University. Tehran - Iran.
Bansal, K.C. and Sharma, R.K. (2003). Chloroplast transformation as a tool for prevention of gene flow from GM crops to weedy or wild relatives. Curr Sci, 84(10): 1286-1287.
Bock, R. (2001). Transgenic plastids in basic research and plant biotechnology. J Mol Biol, 312: 425-438.
Bock, R. and Warzecha, H. (2010). Solar-powered factories for new vaccines and antibiotics. Trends Biotechnol, 28(5): 246-252.
Breyer, D., Goossens, M., Herman, Ph. and Sneyers, M. (2009). Biosafety considerations associated with molecular farming in genetically modified plants. J Med Plants Res, 3(11): 825-838.
Chebolu, S and Daniell, H. (2009). Chloroplast-derived vaccine antigens and biopharmaceuticals: expression, folding, assembly and functionality. Curr Top Microbiol Immunol, 332: 33-54.
Chen, M., Liu, X., Wang, Z., Song, J., Qi, Q and Wang, P.G. (2005). Modification of plant N-glycans processing: the future of producing therapeutic protein by transgenic plants. Med Res Rev, 25(3): 343-360.
Clarke, J.L. and Daniell, H. (2011). Plastid biotechnology for crop production: present status and future perspectives. Plant Mol Biol, 76: 211ñ220.
Daniell, H. (1999). Environmentally friendly approaches to genetic engineering. In Vitro Cell Dev Biol Plant, 35: 361ñ368.
Daniell, H., Chebolu, S., Kumar, Sh., Singleton, M. and Falconer, R. (2005). Chloroplast-derived vaccine antigens and other therapeutic proteins. Vaccine, 23(15): 1779-1783.
Daniell, H., Khan, M.S. and Allison, L. (2002). Milestones in chloroplast genetic engineering: an environmentally friendly era in biotechnology. Trends in Plant Science,7(2): 84-91.
Daniell, H., Streatfield, S.J and Wycoff, K. (2001). Medical molecular farming: production of antibodies, biopharmaceuticals and edible vaccines in plants. Trends Plant Sci, 6(5): 219-226.
Davoodi-Semiromi, A., Schreiber, M., Nalapalli, S., Verma, D., Singh, N.D., Banks, R.K., Chakrabarti, D and Daniell, H. (2010). Chloroplast-derived vaccine antigens confer dual immunity against cholera and malaria by oral or injectable delivery. Plant Biotechnol J, 8: 223ñ242.
Desai, P.N., Shrivastava, N and Padh, H. (2010). Production of heterologous proteins in plants: strategies for optimal expression. Biotechnol Adv, 28(4): 427-435.
Dymyad, S. (2007). VHH antibody gene transfer to canola and regeneration of transgenic plants. M.Sc. thesis. Department of Biotechnology, Faculty of Agriculture, Tarbiat Modarres University. Tehran - Iran.
Fischer, R and Emans, N. (2000). Molecular farming of pharmaceutical proteins. Transgenic Res, 9(4-5): 279-299.
Fischer, R., Drossard, J., Commandeur, U., Schillberg, S and Emans, N. (1999). Towards molecular farming in the future: moving from diagnostic protein and antibody production in microbes to plants. Biotechnol Appl
Biochem, 30(2): 101-108.
Fischer, R., Hoffmann, K., Schillberg, S and Emans, N. (2000). Antibody production by molecular farming in plants. J Biol Regul Homeost Agents, 14(2): 83-92.
Fischer, R., Schillberg, S., Hellwig, S., Twyman, R.M and Drossard, J. (2012). GMP issues for recombinant plantderived pharmaceutical proteins. Biotechnol Adv, 30(2): 434-439.
Flinn, J.E and Zavon, J.A. (2004). Green plants as biofactories for drugs. Biopharm Int, 17: 42ñ49.
Gao, M., Li, Y., Xue, X., Wang, X. and Long, J. (2012). Stable plastid transformation for high-level recombinant protein expression: promises and challenges. Journal of Biomedicine and Biotechnology, Vol 2012, Article ID
158232, 16 pages.
Gleba, Y., Klimyuk, V and Marillonnet, S. (2007). Viral vectors for the expression of proteins in plants. Curr Opin Biotechnol, 18: 134ñ141.
Gomord, V., Fitchette, A.C., Menu-Bouaouiche, L., SaintJore-Dupas, C., Plasson, C., Michaud, D and Faye, L. (2010). Plant-specific glycosylation patterns in the context of therapeutic protein production. Plant
Biotechnol J, 8(5): 564-587.
Hellwig, S., Drossard, J., Twyman, R.M and Fischer, R. (2004). Plant cell cultures for the production of recombinant proteins. Nat Biotechnol, 22(11): 1415- 1422.
Honari, H. (2008). Expression of PA gene from Bacillus antracis in Iranian lettuce (Lactuca sativa). Ph.D. thesis, Department of Plant Breeding, College of Agriculture, Tehran University. Tehran - Iran.
Ismaili, A., Jalali-Javaran, M., Rasaee, M.J., Rahbarizadeh, F and Rajabi-memari, H. (2006). Cloning and expression of recombinant camelid single-domain antibody in tobacco. Iranian Journal of Biotechnology, 4(3):162-168.
Kashani, K., Jalali Javaran, M., Mohebodini, M., Moieni, A and Sheikhi Deh Abadi M. (2012). Regeneration and Agrobacterium-mediated transformation of three potato cultivars (Solanum tuberosum cv. Desiree, Agria and
Marfona) by human proinsulin gene. AJCS 6(7): 1212- 1220.
Ko, K., Ahn, M.H., Song, M., Choo, Y.K., Kim, H.S., Ko, K and Joung, H. (2008). Glyco-engineering of biotherapeutic proteins in plants. Mol Cells, 25(4): 494-503.
Ko, K., Brodzik, R and Steplewski, Z. (2009). Production of antibodies in plants: approaches and perspectives. Curr Top Microbiol Immunol, 332: 55-78.
Krattiger, A. and Mahoney, R.T. (2007). Specific IP issues with molecular pharming: case study of plant-derived vaccines. In Intellectual Property Management in Health and Agricultural Innovation: A Handbook of Best Practices. Volume 2. 2nd edition. Edited by Krattiger, A. Mahoney,
R.T., Nelsen, L., Thomson, J.A., Bennett, A.B., Satyanarayana, K., Graff, G.D., Fernandez, C. and Kowalski, S.P. Oxford, UK: MIHR and Davis, USA: PIPRA. 1809-1817. (Available online at www.ipHandbook.org).
Larrick, J.W., Yu, L., Naftzger, C., Jaiswal, S and Wycoff, K. (2001). Production of secretory IgA antibodies in plants. Biomol Eng, 18(3): 87-94.
Lerouge, P., Bardor, M., Pagny, S., Gomord, V and Faye, L. (2000). N-glycosylation of recombinant pharmaceutical glycoproteins produced in transgenic plants: towards an humanisation of plant N-glycans. Curr Pharm Biotechnol, 1(4): 347-354.
Lugade, A.A., Kalathil, S., Heald, J.L and Thanavala, Y. (2010). Transgenic plant-based oral vaccines. Immunol Invest, 39(4-5): 468-482.
Maliga, P and Bock, R. (2011). Plastid biotechnology: food, fuel, and medicine for the 21st century. Plant Physiol, 155: 1501ñ1510.
Masoumi-Asl, A., Jalali-Javaran, M., Mahbodi, F and Alizadeh, H. (2010). Cloning and expression of tissue plasminogen activator (t-PA) gene in tobacco plants. Scientific Research and Essays, 5(9): 917-922.
Mohebodini, M., Jalali-Javaran, M., Mahboodi, F., Alizadeh, H and Ajhdari, H. (2009). Human proinsulin gene cloning in plant expression vector pCAMBIA1304. 6th National Biotechnology Congress of Iran, Tehran-Iran, 13-15 August 2009.
Naqvi, Sh., Ramessar, K., FarrÈ, G., Sabalza, M., Miralpeix, B., Twyman, R.M., Capell, T., Zhu, Ch. and Christou, P. (2011). High-value products from transgenic maize. Biotechnol Adv, 29: 40ñ53.
Pogue, G.P., Vojdani, F., Palmer, K.E., Hiatt, E., Hume, S., Phelps, J., Long, L., Bohorova, N., Kim, D., Pauly, M., Velasco, J., Whaley, K., Zeitlin, L., Garger, S.J., White, E., Bai, Y., Haydon, H and Bratcher, B. (2010). Production of
pharmaceutical-grade recombinant aprotinin and a monoclonal antibody product using plant-based transient expression systems. Plant Biotechnol J, 8(5):638-654.
Rahimifar, P. (2009). Human IFN gene transfer to canola. M.Sc. thesis. Department of Biotechnology, Aborayhan campus of Tehran University. Tehran - Iran.
Hybridomics, 25: 209-215 Schillberg, S., Emans, N. and Fischer, R. (2002). Antibody molecular pharming in plants and plant cells. Phytochem
Rev, 1: 45ñ54.
Schillberg, S., Fischer, R and Emans, N. (2003). 'Molecular farming' of antibodies in plants. Naturwissenschaften, 90(4): 145-155.
Schillberg, S., Twymanb, R.M and Fischer, R. (2005). Opportunities for recombinant antigen and antibody expression in transgenic plantsótechnology assessment. Vaccine, 23: 1764ñ1769.
Seifi-Nabi-Abad, H. (2009). Extraction and purification of human tissue plasminogen activator from transgenic tobacco plants. M.Sc. thesis. Department of Biotechnology, Faculty of Agriculture, Tarbiat Modarres University. Tehran - Iran.
Sourrouille, C., Marshall, B., LiÈnard, D and Faye, L. (2009). From Neanderthal to nanobiotech: from plant potions to pharming with plant factories. Methods Mol Biol, 483: 1-23.
Spok, A., Twyman, R.M., Fischer, R., Ma, J.K. and Sparrow, P.A. (2008). Evolution of a regulatory framework for pharmaceuticals derived from genetically modified plants. Trends Biotechnol, 26: 506ñ517.
Streatfield, S.J. (2005). Oral hepatitis B vaccine candidates produced and delivered in plant material. Immunol Cell Biol, 83(3): 257-262.
Taheri-javan, N. (2008). Human IFN gene transfer to canola and regeneration of the transgenic plants. M.Sc. thesis. Department of Biotechnology, Faculty of
Agriculture, Tarbiat Modarres University. Tehran - Iran.
Tregoning, J.S., Nixon, P., Kuroda, H., Svab, Z., Clare, S., Bowe, F., Fairweather, N., Ytterberg, J., van Wijk, K.J., Dougan, G and Maliga, P. (2003). Expression of tetanus toxin fragment C in tobacco chloroplasts. Nucleic Acids
Res, 31: 1174ñ1179
Rev, 1: 45ñ54.
Schillberg, S., Fischer, R and Emans, N. (2003). 'Molecular farming' of antibodies in plants. Naturwissenschaften, 90(4): 145-155.
Schillberg, S., Twymanb, R.M and Fischer, R. (2005). Opportunities for recombinant antigen and antibody expression in transgenic plantsótechnology assessment. Vaccine, 23: 1764ñ1769.
Seifi-Nabi-Abad, H. (2009). Extraction and purification of human tissue plasminogen activator from transgenic tobacco plants. M.Sc. thesis. Department of Biotechnology, Faculty of Agriculture, Tarbiat Modarres University. Tehran - Iran.
Sourrouille, C., Marshall, B., LiÈnard, D and Faye, L. (2009). From Neanderthal to nanobiotech: from plant potions to pharming with plant factories. Methods Mol Biol, 483: 1-23.
Spok, A., Twyman, R.M., Fischer, R., Ma, J.K. and Sparrow, P.A. (2008). Evolution of a regulatory framework for pharmaceuticals derived from genetically modified plants. Trends Biotechnol, 26: 506ñ517.
Streatfield, S.J. (2005). Oral hepatitis B vaccine candidates produced and delivered in plant material. Immunol Cell Biol, 83(3): 257-262.
Taheri-javan, N. (2008). Human IFN gene transfer to canola and regeneration of the transgenic plants. M.Sc. thesis. Department of Biotechnology, Faculty of
Agriculture, Tarbiat Modarres University. Tehran - Iran.
Tregoning, J.S., Nixon, P., Kuroda, H., Svab, Z., Clare, S., Bowe, F., Fairweather, N., Ytterberg, J., van Wijk, K.J., Dougan, G and Maliga, P. (2003). Expression of tetanus toxin fragment C in tobacco chloroplasts. Nucleic Acids
Res, 31: 1174ñ1179
)