利用植物生物反应器生产医用蛋白质

121213100272100081ProductionofMedicaIProteinsusingPIantBioIogicaIReactorSUNMeng1SUNing2QIANKai-xian1SHENGui-fang21CollegeofBiologyZhejiangUniversityHangzhou3100272BiotechnologyResearchInstituteChineseAcademyofAgriculturalSciencesBeijing100081AbstractPlantexpressionsystemprovidesacheapandsafemeanstoproducetherapeuticproteins.Inthispaperthedevelopmentsofplant-derivedvaccineantibodiesandbiopharmaceuticalsweredescribed.Thetech-nicalpromiseofimprovingtheexpressinglevelofplants-derivedtherapeuticproteinswasalsodiscussed.KeywordsPlant-expresssystemVaccineRecombinantantibodyPhar[e-mail]11986～19902～41989199056101～311.11990CurtissSpaASpaA78～1811993FMDV19HIV-Ⅰ2021221998Modelska2003365583-589ScientiaAgriculturaSinica11Table1RecombinantvaccineexpressedinplantsYearVaccineantigenTransformedplantsvirusExpressionlevelImmunogenicityandprotectivecapacityRef19907S.mutanssurfaceproteinSpaATobaccoImmunogenicandprotectivetakenorally19920.01%TSP89HepatitisvirusBsurfaceantigenTobaccoImmunogenictakenbyinjection19951.00%TSP10RabiesvirusglycoproteinTomato1995Tobacco0.01%TSP11Escherichiacoliheat-labileenterotoxinPotato0.19%TSPImmunogenicandprotectivetakenorally1996Tobacco0.23%TSP12NorwalkviruscapsidproteinPotato0.37%TSPImmunogenicandprotectivetakenorally1996HIV20RabiesandHIVepitopesAlfalfamosaicImmunogenictakenbyinjectionvirusAMV199722MinkEnteritisvirusepitopesCowpeamosaicProtectivetakenbyinjectionvirusCMV19980.19%TSP13Escherichiacoliheat-labileenterotoxinPotatoImmunogenicandprotectivetakenorally199823RabiesvirussurfaceantigenAMVImmunogenicbyinjectionandorally1998B0.30%TSP14CholeratoxinB-subunitPotatoImmunogenicandprotectivetakenorally1998B0.1%TSP15Humaninsulin-CholeratoxinBPotatoImmunogenictakenorallysubunitfusionprotein1999VP1Alfalfa0.01%FW1617FootandmouthdiseasevirusVP1proteinTMVImmunogenicandprotectivetakenbyinjectionandorally1999Lettuce0.01%FW18HepatitisvirusBsurfaceantigenLupinImmunogenictakenorally2000F0.01%FW24RespiratorysyncytialvirusFproteinTomatoImmunogenictakenorally2000S0.20%TSP25PigTransmissiblegastroenteritisAlfalfaImmunogenictakenbyinjectioncoronavirusSprotein2000VP1B0.07～0.9%26HepatitisCvirusVP1-TMVTSPImmunogenictakenbyinjectioncholeratoxinBsubunitfusionprotein2001B4.1%TSP27choleratoxinBsubunitTobaccochloroplast1TSPTotalsolubleproteinFWFreshweight2310IgA22101.2199728B1150～100g4853621Table2TherapeuticanddiagnosticantibodiesexpressedinplantsYearAntibodynameortypePromoterApplicationandspecificantigenPlantExpressionlevelsRefs1995Guys13sIgA35SDentalcaries500µgg-1FW31CaMV35SStreptococcalantigenTobacco1998CO17-1AIgGColoncancer32TMVsubgenomicpromoterU5CPSurfaceantigenTobacco1998Anti-HSV-2IgG35S33CaMV35SHerpessimplexvirusSoy-bean1999C5-1IgG35SDiagnostic1.0%CaMV35SIgGAnti-humanIgGAlfalfaTSP1999ScFvT84.66ScFvCancertreatment29µgg-1leaves32MaizeubiquitinCarcinoembryonicantigenRice32µgg-1seed1999T84.66IgG35SCancertreatment1.0µgg-1FW32EnhancedCaMV35SpromoterCarcinoembryonicantigenTobacco199938C13ScFvB30µgg-1FW34TMVsubgenomicB-celllymphomaTobaccocoatproteinpromotertreamentidiotypevaccine2000ScFvT84.66ScFv0.9µgg-1leaves32MaizeubiquitinCancertreatmentWheat1.5µgg-1seedCarcinoembryonicantigen1TMVtobaccomosaicvirusCaMVCowpeamosaicvirus350gLT-B10LT-BLT-BLT-B106LT-BⅠⅡ10mU29322.11056IgGIgAIgGIgAIgAsIgAsingle-chainantibodyfragmentScFvfragmentantigenbindingheavy-chainvariabledomainsVaquero3022.24IgG-IgAIgG3132Anti-HSV-2HSV-2335855ScFvB34Daniell250m2IgG500～6005000320.05%FW50/1000/100/33.1HAS550tHAS233IL-2IL-4353Table3PharmaceuticalproteinsexpressedinplantsYearProteinnameApplicationorindicationPlanthostExpressionlevelsRefs1989αHumaninterferonαRiceNotreport3βHumaninterferonβHepatitisBandCtreatmentTobacco0.01%FW1990Humanserumalbumin0.02%TSP4LivercirrhosisburnssurgerytreatmentTobacco19930.01%TSP23HumanepidermalgrowthWoundrepairandcellproliferationTobacco1994α-2.00%TSP36α-TricosanthinHIVtherapiesTMV19953%seedproteinSP37HumanhirudinThrombininhibitorCanola19950.01%TSP23HumanerythropoietinAnemiatreatmentTobacco199523Humangranulocyte-macro-phageNeutropeniaTobaccocolony-stimulatingfactor19961.00%-10.00%TSP38GlucocerebrosidaseGaucherdiseaseTobacco19960.10%SP39HumanenkephalinsAntehyperanalgesicArabidopsis1996CHumanproteinCAnticoagulantTobacco0.01%TSP231997αβ0.05%SP23HumanhemoglobinαβBloodsubstituteTobacco1999α-1-23Humanα-1-antitrypsinCysticfibrosisliverdiseaseandhemorrhageRice199940HumanaprotininTrypsininhibitorMaize20000.01%FW41HumanhomotrimericcollagenCollagenTobacco20000.10%TSP42HumanlactoferrinAntimicrobialPotato20007.00%TSP43HumansomatotropinGrowthhormonetreatmentTobaccochloroplast685363.2Cramer38AppliedPhytologicsα-1-α-1-1998200437AvidinHoodAvidinα-230mgAvidin44β-4541%4.1MasonB134.2BCTB3'-SEKDEL464.3B1mgLT-B32MasonPatatinNorwalkvgiruscapsidproteinNVCPNVCP0.37%124.410010010000Staub7%4378555.1%4721References1GiddingsGAllisonGBrooksDCarterA.Transgenicplantsasfactoriesforbiopharmaceuticals.Nat.Biotechnol200018111151-1155.2BartaASommergruberKThompsonDHartmuthKMatzkeMMatzkeA.Theexpres