DOI QR코드

DOI QR Code

형질전환 식물세포배양을 이용한 바이오의약품 생산

Production of biopharmaceuticals in transgenic plant cell suspension cultures

  • Kwon, Jun-Young (Department of Biological Engineering, Inha University) ;
  • Cheon, Su-Hwan (Department of Biological Engineering, Inha University) ;
  • Lee, Hye-Ran (Department of Biological Engineering, Inha University) ;
  • Han, Ji-Yeon (Department of Biological Engineering, Inha University) ;
  • Kim, Dong-Il (Department of Biological Engineering, Inha University)
  • 발행 : 2009.12.31

초록

Transgenic plant cell cultures for the production of biopharmaceuticals including monoclonal antibodies, recombinant proteins have been regarded as an alternative platform in addition to traditional microbial fermentation and mammalian cell cultures. Plant-made pharmaceuticals (PMPs) have several advantages such as safety, cost-effectiveness, scalability and possibility of complex post-translational modifications. Increasing demand for the quantity and diversity of pharmaceutical proteins may accelerate the industrialization of PMP technology. Up to date, there is no plant-made recombinant protein approved by USFDA (Food and Drug Administration) for human therapeutic uses due to the technological bottlenecks of low expression level and slight differences in glycosylation. Regarding expression levels, it is possible to improve the productivity by using stronger promoter and optimizing culture processes. In terms of glycosylation, humanization has been attempted in many ways to reduce immune responses and to enhance the efficacy as well as stability. In this review article, all these respects of transgenic plant cell cultures were summarized. In addition, we also discuss the general characteristics of plant cell suspension cultures related with bioreactor design and operation to achieve high productivity in large scale which could be a key to successful commercialization of PMPs.

키워드

참고문헌

  1. Abdullah MA, Ariff AB, Marziah M, Ali AM, Lajis NH (2000) Strategies to overcome foaming and wall-growth during the cultivation of Morinda elliptica cell suspension culture in a stirred-tank bioreactor. Plant Cell Tiss Org Cult 60:205-212 https://doi.org/10.1023/A:1006495107778
  2. Aviezer D, Brill-Almon E, Shaaltiel Y, Hashmueli S, Bartfeld D, Mizrachi S, Liberman Y, Freeman A, Zimran A, Galun E (2009) A plant-derived recombinant human glucocerebrosidase enzyme: A preclinical and phase I investigation. Plos Med 4: 1-5 https://doi.org/10.1371/journal.pmed.0040001
  3. Bakker H, Bardor M, Molthoff JW, Gomord V, Elvers I, Stevens LH, Jordi W, Lommen A, Faye L, Lerouge P, Bosch D (2001) Galactose-extended glycans of antibodies produced by transgenic plants. Proc Natl Acad Sci USA 98:2899-2904 https://doi.org/10.1073/pnas.031419998
  4. Barnes LM, Dickson AJ (2006) Mammalian cell factories for efficient and stable protein expression. Curr Opinion Biotechnol 17:381-386 https://doi.org/10.1016/j.copbio.2006.06.005
  5. Betts JI, Baganz F (2006) Miniature bioreactors: current practices and future opportunities. Microb Cell Fact 5:21-34 https://doi.org/10.1186/1475-2859-5-21
  6. Bohme C, Schroder MB, JungHeiliger H, Lehmann J (1997) Plant cell suspension culture in a bench-scale fermenter with a newly designed membrane stirrer for bubble-free aeration. Appl Microbiol Biotechnol 48:149-154 https://doi.org/10.1007/s002530051030
  7. Castilho A, Pabst M, Leonard R, Veit C, Altmann F, Mach L, Glossl J, Strasser R, Steinkellner H (2008) Construction of a functional CMP-sialic acid (CMP-Neu5Ac) biosynthesis pathway in Arabidopsis thaliana. Plant Physiol 147:331-339 https://doi.org/10.1104/pp.108.117572
  8. Doran PM (1999) Design of mixing systems for plant cell suspensions in stirred reactors. Biotechnol Prog 15:319-335 https://doi.org/10.1021/bp990042v
  9. Doran PM (2006) Foreign protein degradation and instability in plants and plant tissue cultures. Trends Biotechnol 24: 426-432 https://doi.org/10.1016/j.tibtech.2006.06.012
  10. Eibl R, Eibl D (2008) Design of bioreactors suitable for plant cell and tissue cultures. Phytochem Rev 7:593-598 https://doi.org/10.1007/s11101-007-9083-z
  11. Fox JL (2006) Turning plants into protein factories. Nat Biotechnol 24:1191-1193 https://doi.org/10.1038/nbt1006-1191
  12. Gill NK, Appleton M, Baganz F, Lye GJ (2008) Quantification of power consumption and oxygen transfer characteristics of a stirred miniature bioreactor for predictive fermentation scaleup. Biotechnol Bioeng 100:1144-1155 https://doi.org/10.1002/bit.21852
  13. Girard LS, Fabis MJ, Bastin M, Courtois D, Petiard V, Koprowski H (2006) Expression of a human anti-virus monoclonal antibody in tobacco cell culture. Biochem Biophys Res Comm 345:602-607 https://doi.org/10.1016/j.bbrc.2006.03.219
  14. Gomord V, Faye L (2004) Posttranslational modification of therapeutic proteins in plants. Curr Opin Plant Biol 7:171-181 https://doi.org/10.1016/j.pbi.2004.01.015
  15. Gotoh T, Miyazaki Y, Sato W, Kikuchi K, Bentley WE (2001) Proteolytic activity and recombinant protein production in virus-infected Sf-9 insect cell cultures supplemented with carboxyl and cysteine protease inhibitors. J Biosci Bioeng 92: 248-255 https://doi.org/10.1263/jbb.92.248
  16. Huang TK, McDonald KA (2009) Bioreactor engineering for recombinant protein production in plant cell suspension cultures. Biochem Eng J 45:168-184 https://doi.org/10.1016/j.bej.2009.02.008
  17. Huang TK, Plesha MA, Falk BW, Dandekar AM, Mcdonald KA (2009) Bioreactor strategies for improving production yield and functionality of a recombinant human protein in transgenic tobacco cell cultures. Biotechnol Bioeng 102:508-520 https://doi.org/10.1002/bit.22061
  18. Jefferis R (2009) Glycosylation as a strategy to improve antibody-based therapeutics. Nat Drug Discov 8:226-234 https://doi.org/10.1038/nrd2804
  19. Kwon TH, Kin YS, Lee JH, Yang MS (2003) Production and secretion of biologically active human granulocyte-macrophage colony stimulating factor in transgenic tomato suspension cultures. Biotechnol Lett 25:1571-1574 https://doi.org/10.1023/A:1025409927790
  20. Lee SJ, Park CI, Park MY, Jung HS, Ryu WS, Lim SM, Tan HK, Kwon TH, Yang MS, Kim DI (2007) Production and characterization of human CTLA4Ig expressed in transgenic rice cell suspension cultures. Protein Expr Purif 51:293-302 https://doi.org/10.1016/j.pep.2006.08.019
  21. Lerouge P, Bardor M, Pagny S, Gomord V, Faye L (2000) N-glycosylation of recombinant pharmaceutical glycoproteins produced in transgenic plants: towards an humanisation of plant N-glycans. Curr Pharm Biotechnol 1:347-354 https://doi.org/10.2174/1389201003378843
  22. Mandenius CF, Brundin A (2008) Bioprocess optimization using design-of-experiments methodology. Biotechnol Prog 24: 1191-1203 https://doi.org/10.1002/btpr.67
  23. Miele L (1997) Plants as bioreactors for biopharmaceutical: regulatory considerations. Trends Biotechnol 15:45-50 https://doi.org/10.1016/S0167-7799(97)84202-3
  24. Misaki R, Kimura Y, Palacpac NQ, Yoshida S, Fujiyama K, Seki T (2003) Plant cultured cells expressing human b1,4-galactosyltransferase secrete glycoproteins with galactoseextended N-linked glycans. Glycobiology 13:199-205 https://doi.org/10.1093/glycob/cwg021
  25. Pervin B, Emilio RC (2008) Plant molecular farming: Opportunities and challenges. Crit Rev Biotechnol 28:153-172 https://doi.org/10.1080/07388550802046624
  26. Raposo S, Lima-Costa ME (2006) Rheology and shear stress of Centaurea calcitrapa cell suspension cultures grown in bioreactor. Biotechnol Lett 28:431-438 https://doi.org/10.1007/s10529-005-6181-0
  27. Ritala A, Wahlstro EH, Holkeri MH, Hafren A, Makelainen K, Baez J, Makinen K, Nuutila AM (2008) Production of a recombinant industrial protein using barley cell cultures. Protein Expr Purif 59:274-281 https://doi.org/10.1016/j.pep.2008.02.013
  28. Roberts SG, Shuler ML (1997) Large-scale plant cell culture. Curr Opinion Biotechnol 8:154-159 https://doi.org/10.1016/S0958-1669(97)80094-8
  29. Shinmyo A, Shoji T, Bando E, Nagaya S, Nakai Y, Kato K, Sekine M, Yoshida K (1998) Metabolic engineering of cultured tobacco cells. Biotechnol Bioeng 58:329-332 https://doi.org/10.1002/(SICI)1097-0290(19980420)58:2/3<329::AID-BIT34>3.0.CO;2-4
  30. Sowana DD, Williams DRG, Dunlop EH, Dally BB, O'Neill BK, Fletcher DF (2001) Turbulent shear stress effects on plant cell suspension cultures. Trans I Chem E 79:867-875 https://doi.org/10.1205/02638760152721370
  31. Strasser R, Altmann F, Mach L, Glossl J, Steinkellner H (2004) Generation of Arabidopsis thaliana plants with complex N-glycans lacking b1,2-linked xylose and core a1,3-linked fucose. FEBS Letters. 561:132-136 https://doi.org/10.1016/S0014-5793(04)00150-4
  32. Taticek RA, Legge RL (1991) The scale-up of plant cell culture: engineering considerations. Plant Cell Tiss Organ Cult 24: 139-159 https://doi.org/10.1007/BF00039742
  33. Terashima M, Murai Y, Kawamura M, Nakanishi S, Stoltz T, Chen L, Drohan W, Rodriguez RL, Kotoh S (1999) Production of functional human a1-antitrypsin by plant cell culture. Appl Microbiol Biotechnol 52:516-523 https://doi.org/10.1007/s002530051554
  34. Terashima M, Ejiri Y, Hashikawa N, Yoshida H (2000) Effect of sugar concentration of recombinant human a1-antitrypsin production by genetically engineered rice cell. Biochem Eng J 6:201-205 https://doi.org/10.1016/S1369-703X(00)00088-7
  35. Terashima M, Ejiri Y, Hashikawa N, Yoshida H (2001) Utilization of an alternative carbon source for efficient production of human a1-antitrypsin by genetically engineered rice cell culture. Biotechnol Prog 17:403-406 https://doi.org/10.1021/bp010024p
  36. Terashima M, Hashikawa N, Hattori M, Yoshida H (2002) Growth charateristic of rice cell genentically modified for recombinant human a1-antitrypsin production. Biochem Eng J 12: 155-160 https://doi.org/10.1016/S1369-703X(02)00064-5
  37. Trexler MM, Mcdonald KA, Jackman AP (2005) A cyclical semicontinuous process for production of human a1-antitrypsin using metabolically induced plant cell suspension cultures. Biotechnol Prog 21:321-328 https://doi.org/10.1021/bp0498692
  38. Tsoi, BM, Doran PM (2002) Effect of medium properties and additives on antibody stability and accumulation in suspended plant cell cultures. Biotechnol Appl Biochem 35: 171-180 https://doi.org/10.1042/BA20010105
  39. Twyman RM, Stoger E, Schillberg S, Christou P, Fischer R (2003) Molecular farming in plants: Host systems and expression technology. Trends Biotechnol 21:570-578 https://doi.org/10.1016/j.tibtech.2003.10.002
  40. Wang PM, Huang TK, Cheng HP, Chien YH, Wu WT (2002) A modified airlift reactor with high capabilities of liquid mixing and mass transfer. J Chem Eng Jpn 35:354-359 https://doi.org/10.1252/jcej.35.354
  41. Warzecha H (2008) Biopharmaceuticals from plants: a multitude of options for posttranslational modifications. Biotechnol Genetic Eng Rev 25:315-330 https://doi.org/10.5661/bger-25-315
  42. Williams GRC, Doran PM (2000) Hairy root culture in a liquiddispersed bioreactor: Characterization of spatial heterogeneity. Biotechnol Prog 16:391-401 https://doi.org/10.1021/bp0000306
  43. Yin JC, Li GX, Ren XF, Herrler G (2007) Select what you need: a comparative evaluation of the advantages and limitations of frequently used expression systems for foreign genes. J Biotechnol 127:335-347 https://doi.org/10.1016/j.jbiotec.2006.07.012
  44. Zhang S, Handa-Corrigan A, Spier RE (1992) Foaming and media surfactant effects on the cultivation of animal cells in stirred and sparged bioreactors. J Biotechnol 25:289-306 https://doi.org/10.1016/0168-1656(92)90162-3
  45. Zhong JJ, Yu JT, Yoshida T (1995) Recent advance in plant cell cultures in bioreactors. World J Microbiol Biotechnol 11: 461-467 https://doi.org/10.1007/BF00364621
  46. Zhong JJ, Chen F, Hu WW (1999) High density cultivation of Panax notoginseng cells in stirred bioreactor for the production of ginseng biomass and ginseng saponin. Process Biochem 35:491-496 https://doi.org/10.1016/S0032-9592(99)00095-3

피인용 문헌

  1. Enhanced productivity of biomass and bioactive compounds through bioreactor cultures of Eleutherococcus koreanum Nakai adventitious roots affected by medium salt strength vol.36, pp.1, 2012, https://doi.org/10.1016/j.indcrop.2011.10.033
  2. Effect of nitrogen source on biomass and bioactive compound production in submerged cultures of Eleutherococcus koreanum nakai adventitious roots vol.28, pp.2, 2012, https://doi.org/10.1002/btpr.1506
  3. Autophagy: Noble target mechanisms in natural medicines as anticancer agents vol.37, pp.1, 2010, https://doi.org/10.5010/JPB.2010.37.1.057
  4. Plants as platforms for the production of vaccine antigens vol.37, pp.3, 2010, https://doi.org/10.5010/JPB.2010.37.3.250
  5. Soil Acclimatization of Regenerated Plants by Gibberellic Acid Treatments of Panax ginseng C. A. Meyer vol.26, pp.1, 2013, https://doi.org/10.7732/kjpr.2013.26.1.084