CHO细胞表达系统研究进展_郑惠惠

201664239～243CurrentBiotechnologyISSN2095-2341櫅櫅櫅櫅櫅櫅櫅櫅櫅櫅櫅櫅櫅櫅殯殯殯殯Ｒeviews2016-02-222016-04-04。[e-mail]。*。[e-mail]*141017CHO。、CHO、。CHOCHO。、CHO、CHOCHO。CHODOI10．3969/j．issn．2095－2341．2016．04．03ProgressofCHOExpressionSystemZHENGHui-huiJIANGHong*BeijingWondergenBio-medicineTechnologyCo．Ltd．Beijing141017ChinaAbstractCHOcellexpressionsystemisthepreferredsystemforrecombinantglycoproteinproduction．Withtheevolvingdevelopmentandapplicationsofserum－freesuspensionculturetechnologygeneticengineeringandthelarge-scaleculturetechnologiesCHOcellexpressionsystemhasbecomethemostimportantexpressionorproductionsystemofbiotechnologyproducts．Thissystemiswidelyusedintheresearchandproductionofantibodiesrecombinantproteinsandvaccines．Inrecentyearsresearchershavemadegreateffortstoimprovetheexpressionandlarge-scaleproductionofrecombinantproteinsbyusinglatestbioengineeringtechnologyandthedevelopmentoftherecombinantproteinexpressionmechanism．ThisarticlebrieflyreviewedtherecentdevelopmentoftheCHOcellexpressionsysteminthreeaspectstheoptimizationoftheculturemediumconstructionofengineeredCHOstrainsforhigh-levelproductionandlarge-scalecultureresearchwhichwasexpectedtoprovidereferenceforresearchandapplicationofCHOcellexpressionsystem．KeywordsCHOcellculturecellengineeringrecombinantantigenexpressionCHOPuck1957。CHO。、、、CHO、、。CHO。、。CHO、。、CHO。、、、。、CHO、CHOCHO。1。CHOCHO。、、。。Davami1DG44。2。134。。CHO5。6Plackett-Burman、11G-S。4．12×106cells/mL。Xu7Plackett-BurmanSVM、BSACHO-K1。7．0×106cells/mL8。Miki9IGF-1LPACHO。CHO。CHOCHO。CHO、、。、CHOCHO。2CHOCHO。、、。。2．1。Zhou10siＲNAALDHaPDHKs90%。Toussaint11rCHOPYC2。2．2CHO。Majos12CHO1Asp29Asn。Cost13BCL2XBAXBAK5。Ｒitter148。2．3。LeFourn15CHOSＲP14042CurrentBiotechnology。Peng16SLY1、MUNC18CXBP1IgG20Ｒahimpour17CHOCEＲTt-PA35%。2．4CHON-。Goh18N-ICHO-gmt4。Zhang19CHO-gmt5FcN-ADCC。CHO-K1Yang20ZFNs19N-、、LacNAc、N-N-。CHO。、、。3、。CHO1000LCHO。。、。、。3．1、、pH、、CO2、。、。Fan21CHO、IgGN-。Kim22IgG2．3g/L。WGHt-PA422mg/L23。3．2。。24u-PADNACHOCytopore。u-PA10。Ventini25CytodexCHO-hTSHrhTSH。26CHOCHOMK3-A2rhTNK-tPA89mg/L·d。3．3F68。F680．05%0．075%500kDaγPGAF68CHODG4427。。pH、、。142CHO4CHO。、、、CHO。CHO、、、。、、、。。、、。、CHO。1DavamiFEghbalpourFNematollahiLetal．．EffectsofpeptonesupplementationindifferentculturemediaongrowthmetabolicpathwayandproductivityofCHODG44cellsanewinsightintoaminoacidprofilesJ．Iran．Biomed．J．2015194194－205．2SungYHLimSWChungJYetal．．Yeasthydrolysateasalow-costadditivetoserum-freemediumfortheproductionofhumanthrombopoietininsuspensionculturesofChinesehamsterovarycellsJ．Appl．Microbiol．Biotechnol．2004635527－536．3DavamiFBaldiLＲajendraYetal．．PeptonesupplementationofculturemediumhasvariableeffectsontheproductivityofCHOcellsJ．Int．J．Mol．CellMed．201433146－156．4ChunBHKimJHLeeHJetal．．Usabilityofsize-excludedfractionsofsoyproteinhydrolysatesforgrowthandviabilityofChinesehamsterovarycellsinprotein-freesuspensioncultureJ．Bioresour．Technol．20079851000－1005．5CHOJ．2011101152－1156．6CHOJ．2010185－92．7XuJYanFＲLiZHetal．．Serum-freemediumoptimizationbasedontrialdesignandsupportvectorregressionJ．Biomed．Ｒes．Int．2014doi10．1155/2014/269305．8EberhardySＲＲadzniakLLiuZ．IronIIIcitrateinhibitspolyethylenimine-mediatedtransienttransfectionofChinesehamsterovarycellsinserum-freemediumJ．Cytotechnology2009601－9．9MikiHTakagiM．Designofserum－freemediumforsuspensioncultureofCHOcellsonthebasisofgeneralcommercialmediaJ．Cytotechnology2015674689－697．10ZhouMCrawfordYNgDetal．．DecreasinglactatelevelandincreasingantibodyproductioninChineseHamsterOvarycellsCHObyreducingtheexpressionoflactatedehydrogenaseandpyruvatedehydrogenasekinasesJ．J．Biotechnol．20111531－227－34．11ToussaintCHenryODurocherY．MetabolicengineeringofCHOcellstoalterlactatemetabolismduringfed－batchculturesJ．J．Biotechnol．2015217122－131．12MajorsBSChiangGGPedersonNEetal．．Directedevolutionofmammaliananti-apoptosisproteinsbysomatichypermutationJ．ProteinEng．Des．Sel．201225127－38．13CostGJFreyvertYVafiadisAetal．．BAKandBAXdeletionusingzinc-fingernucleasesyieldsapoptosis-resistantCHOcellsJ．Biotechnol．Bioeng．20101052330－40．14ＲitterAVoedischBWienbergJetal．．Deletionofatelomericregiononchromosome8correlateswithhigherproductivityandstabilityofCHOcelllinesJ．Biotechnol．Bioeng．201611351084－1093．15LeFournVGirodPABucetaMetal．．CHOcellengineeringtopreventpolypeptideaggregationandimprovetherapeuticproteinsecretionJ．Metab．Eng．20142191－102．16PengＲWFusseneggerM．MolecularengineeringofexocyticvesicletrafficenhancestheproductivityofChinesehamsterovarycellsJ．Biotechnol．Bioeng．200910241170－1181．17ＲahimpourAVaziriBMoazzamiＲetal．．EngineeringthecellularproteinsecretorypathwayforenhancementofrecombinanttissueplasminogenactivatorexpressioninChinesehamsterovarycellseffectsofCEＲTandXBP1sgenesJ．J．Microbiol．Biotechnol．20132381116－1122．18GohJSLiuYChanKFetal．．ProducingrecombinanttherapeuticglycoproteinswithenhancedsialylationusingCHO-242CurrentBiotechnologygmt4glycosylationmutantcellsJ．Bioengineered201454269－273．19ZhangPHaryadiＲChanKFetal．．IdentificationoffunctionalelementsoftheGDP-fucosetransporterSLC35C1usinganovelChinesehamsterovarymutantJ．Glycobiology2012227897