烟草生物反应器生产药用蛋白的研究进展

doi:10.11924/j.issn.1000-6850.2014-1855

摘要/Abstract

摘要： 总结了烟草生物反应器生产药用蛋白的3种类型，归纳了细胞核表达、叶绿体表达以及瞬时表达等外源重组蛋白的表达体系，重点阐述了利用烟草表达自身抗原的口服免疫耐受诱导，进而提出了烟草生物反应研究存在的问题与解决方法。通过上述分析，对下一步利用烟草生物反应器生产药用蛋白及其在中国烟草控制规划中的应用前景进行了展望。

关键词: 施肥, 施肥, 光照强度, 野老鹳草, 大巢菜, 种子萌发, 竞争

Abstract: This article reviewed three main kinds of therapeutic proteins produced by tobacco bioreactors, concluded the expression systems producing exogenous recombinant protein including nuclear expression, chloroplast expression and transient expression, and highlighted oral tolerance induction using tobacco expressing autoantigens, accordingly this article raised the problems to be solved in tobacco bioreactor research and the solutions. From above analysis, prospect was made for further improvement of tobacco bioreactor for production of pharmaceutical proteins and its application in China's tobacco control programs.

闫宁,刘艳华,张忠锋. 烟草生物反应器生产药用蛋白的研究进展[J]. 中国农学通报, 2014, 30(31): 57-63.

参考文献

[1] Horn M E, Woodard S L, Howard J A. Plant molecular farming: systems and products[J]. Plant Cell Rep,2004,22(10):711-720.
[2] Goldstein D A, Thomas J A. Biopharma- ceuticals derived from genetically modified plants[J]. Int J Med,2004,97(11):705-716.
[3] Hiatt A, Cafferkey R, Bowdish K. Production of antibodies in transgenic plants[J]. Nature,1989,342(6245):76-78.
[4] Johansen F E, Pekna M, Norderhaug I N, et al. Absence of epithelial immunoglobulin A transport, with increased mucosal leakiness, in polymeric immunoglobulin receptor/secretory component-deficient mice[J]. J Exp Med,1999,190(7):915-922.
[5] Ma J K C, Hiatt A, Hein M, et al. Generation and assembly of secretory antibodies in plants[J]. Science,1995,268(5211):716-719.
[6] Ma J K C, Hikmat B Y, Wycoff K, et al. Characterization of a recombinant plant monoclonal secretory antibody and preventive immunotherapy in humans[J]. Nat Med,1998,4(5):601-606.
[7] Pogrebnyak N, Golovkin M, Andrianov V, et al. Severe acute respiratory syndrome (SARS) S protein production in plants: development of recombinant vaccine[J]. Proc Natl Acad Sci USA, 2005,102(25):9062-9067.
[8] Golovkin M, Spitsin S, Andrianov V, et al. Smallpox subunit vaccine produced in planta confers protection in mice[J]. Proc Natl Acad Sci USA,2007,104(16):6864-6869.
[9] Vermij P, Waltz E. USDA approves the first plant-based vaccine[J]. Nat Biotechnol,2006(24):233-234.
[10] 张保龙,杨郁文,倪万潮,等.转H5禽流感病毒M2e基因烟草的研究[J].江苏农业学报,2010,26(1):51-54.
[11] McCormick A A, Reddy S, Reinl S J, et al. Plant produced idiotype vaccines for the treatment of non-Hodgkin's lymphoma: safety and immunogenicity in a phase I clinical study[J]. Proc Natl Acad Sci USA,2008,105(29):10131-10136.
[12] 张辉.烟草也可用来治疗癌症[J].中国烟草科学,2012,33(4):108.
[13] Parkin J, Cohen B. An overview of the immune system[J]. Lancet, 2001,357(9270):1777-1789.
[14] Thomson A W, Lotze M T. The cytokine handbook[M]. Boston: Academic Press,2003.
[15] Papaetis G S, Karapanagiotou L M, Pandha H, et al. Targeted therapy for advanced renal cell cancer: cytokines and beyond[J]. Curr Pharm Des,2008,14(22):2229-2251.
[16] Thompson J P, Debinski W. Mutants of interleukin 13 with altered reactivity toward interleukin 13 receptors[J]. J Biol Chem,1999,274 (42):29944-29950.
[17] Eisenmesser E Z, Kapust R B, Nawrocki J P, et al. Expression, purification, refolding, and characterization of recombinant human interleukin- 13: utilization of intracellular processing[J]. Protein Expr Purif,2000,20(2):186-195.
[18] Cannon-Carlson S, Varnerin J, Tsarbopoulos A, et al. Expression,purification, and characterization of recombinant human interleukin- 13 from NS-0 cells[J]. Protein Expr Purif,1998,12(2):239-248.
[19] Wang D J, Brandsma M, Yin Z Q, et al. A novel platform for biologically active recombinant human interleukin- 13 production [J]. Plant Biotechnol J,2008,6(5):504-515.
[20] 蒋世翠,王义,李校堃,等.酸性成纤维细胞生长因子植物表达载体的构建及转化烟草的初步研究[J].生物医学工程杂志,2010,27(1): 126-131.
[21] 陈宇,刘孝菊,薛萍,等.在烟草中瞬时表达人角质细胞生长因子 1 [J].中国生物制品学杂志,2011,24(10):1144-1147.
[22] 李源,李海权,肖刚,等.利用烟草表达人源性胰岛素样生长因子 1 [J].植物研究,2011,31(3):336-340.
[23] 梁宏伟,陈发菊,王玉兵,等.利用转基因烟草表达人胰高血糖素样肽 1的研究[J].生物技术通报,2013(1):139-143.
[24] Weiner H L. Oral tolerance for the treatment of autoimmune diseases[J]. Annu Rev Med,1997(48):341-351.
[25] Mowat A M. The regulation of immune-responses to dietary-protein antigens[J]. Immunol Today,1987,8(3):93-98.
[26] Faria A M C, Weiner H L. Oral tolerance[J]. Immunol Rev,2005,206 (1):232-259.
[27] Masteller E L, Bluestone J A. Immunotherapy of insulin-dependent diabetes mellitus[J]. Curr Opin Immunol,2002,14(5):652-659.
[28] Elliott J F, Qin H Y, Bhatti S, et al. Immunization with the larger isoform of mouse glutamic-acid decarboxylase (GAD(67)) prevents autoimmune diabetes in NOD mice[J]. Diabetes,1994,43(12):1494- 1499.
[29] Ma S, Zhao D L, Yin Z Q, et al. Transgenic plants expressing autoantigens fed to mice to induce oral immune tolerance[J]. Nat Med,1997,3(7):793-796.
[30] Ma S, Huang Y, Yin Z, et al. Induction of oral tolerance to prevent diabetes with transgenic plants requires glutamic acid decarboxylase (GAD) and IL-4[J]. Proc Natl Acad Sci USA,2004, 101(15):5680-5685.
[31] Davoodi-Semiromi A, Samson N, Daniell H. The green vaccine: a global strategy to combat infectious and autoimmune diseases[J]. Hum Vaccin,2009,5(7):488-493.
[32] Arlen P A, Singleton M, Adamovicz J J, et al. Effective plague vaccination via oral delivery of plant cells expressing F1-V antigens in chloroplasts[J]. Infect Immun,2008,76(8):3640-3650.
[33] Mosmann T R, Coffman R L. TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties[J]. Annu Rev Immunol,1989(7):145-173.
[34] Ruhlman T, Ahangari R, Devine A, et al. Expression of cholera toxin Bproinsulin fusion protein in lettuce and tobacco chloroplasts—oral administration protects against development of insulitis in non-obese diabetic mice[J]. Plant Biotechnol J,2007,5(4): 495-510.
[35] Gonzalez-Rabade N, McGowan EG, Zhou F, et al. Immunogenicity of chloroplast- derived HIV- 1 p24 and a p24- Nef fusion protein following subcutaneous and oral administration in mice[J]. Plant Biotechnol J,2011,9(6):629-638.
[36] Kanamoto H, Yamashita A, Asao H, et al. Efficient and stable transformation of Lactuca sativa L. cv Cisco (lettuce) plastids[J]. Transgenic Res,2006,15(2):205-217.
[37] Zhou F, Badillo-Corona JA, Karcher D, et al. High-level expression of human immunodeficiency virus antigens from the tobacco and tomato plastid genomes[J]. Plant Biotechnol J,2008,6(9):897-913.
[38] Limaye A, Koya V, Samsam M, et al. Receptor- mediated oral delivery of a bioencapsulated green fluorescent protein expressed in transgenic chloroplasts into the mouse circulatory system[J]. FASEB J,2006,20(7):959-961.
[39] Streatfield SJ. Approaches to achieve high- level heterologous protein production in plants[J]. Plant Biotechnol J,2007,5(1):2-15.
[40] Benchabane M, Goulet C, Rivard D, et al. Preventing unintended proteolysis in plant protein biofactories[J]. Plant Biotechnol J,2008, 6(7):633-648.
[41] Torrent M, Llompart B, Lasserre- Ramassamy S, et al. Eukaryotic protein production in designed storage organelles[J]. BMC Biol, 2009(7):14.
[42] Torrent M, Llop- Tous I, Ludevid M D. Protein body induction: a new tool to produce and recover recombinant proteins in plants[M]. Totowa: Humana Press Inc: Methods in molecular biology,2009 (483):193-208.
[43] Patel J, Zhu H, Menassa R, et al. Elastin- like polypeptide fusions enhance the accumulation of recombinant proteins in tobacco leaves [J]. Transgenic Res,2007,16(2):239-249.
[44] Maliga P. Plastid transformation in higher plants[J]. Annu Rev Plant Biol,2004(55):289-313.
[45] Grevich J J, Daniell H. Chloroplast genetic engineering: recent advances and future perspectives[J]. Crit Rev Plant Sci,2005,24(2): 83-107.
[46] Gisby M F, Mellors P, Madesis P, et al. A synthetic gene increases TGFβ3 accumulation by 75- fold in tobacco chloroplasts enabling rapid purification and folding into a biologically active molecule[J]. Plant Biotechnol J,2011,9(5):618-628.
[47] Bally J, Nadai M, Vitel M, et al. Plant physiological adaptations to the massive foreign protein synthesis occurring in recombinant chloroplasts[J]. Plant Physiol,2009,150(3):1474-1481.
[48] Molina A, Hervas-Stubbs S, Daniell H, et al. High yield expression of a viral peptide animal vaccine in transgenic tobacco chloroplasts [J]. Plant Biotechnol J,2004,2(2):141-153.
[49] Ruf S, Karcher D, Bock R. Determining the transgene containment level provided by chloroplast transformation[J]. Proc Natl Acad Sci USA,2007,104(17):6998-7002.
[50] Daniell H, Kumar S, Dufourmantel N. Breakthrough in chloroplast genetic engineering of agronomically important crops[J]. Trends Biotechnol,2005,23(5):238-245.
[51] Rice J, Ainley W M, Shewen P. Plant-made vaccines: biotechnology and immunology in animal health[J]. Anim Health Res Rev,2005,6 (2):199-209.
[52] Day A, Goldschmidt- Clermont M. The chloroplast transformation toolbox: selectable markers and marker removal[J]. Plant Biotechnol J,2011,9(5):540-553.
[53] Gleba Y, Klimyuk V, Marillonnet S. Magnifection- a new platform for expressing recombinant vaccines in plants[J]. Vaccine,2005,23 (17-18):2042-2048.
[54] 钟雪,齐广勋,康岭生,等.利用植物叶绿体表达重组药用蛋白和疫苗研究进展[J].农业生物技术学报,2012,20(9):1080-1096.
[55] Corneille S, Lutz K, Svab Z, et al. Efficient elimination of selectable markergenes from the plastid genome by the CRE- lox site-specific recombination system[J]. Plant J,2001,27(2):171-178.
[56] Azhakanandam K, Weissinger SM, Nicholson JS, et al. Ampliconplus Targeting Technology (APTT) for rapid production of a highly unstable vaccine protein in tobacco plants[J]. Plant Mol Biol,2007, 63(3):393-404.
[57] 莫倩珍,麦荣嘉,杨志晓,等.快速高效植物瞬时表达的实验室烟草无土栽培体系的构建[J].南方医科大学学报,2012,32(6):772-777.
[58] 贾士荣.转基因植物的环境及食品安全性[J].生物工程进展,2009, 17(6):37-42.
[59] 中国烟草控制规划(2012-2015 年)[J].慢性病学杂志,2013,14(3): 161-168.