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1、PlantBiotechnologyJournal(2015)13,pp.1199–1208doi:10.1111/pbi.12428ReviewarticleLarge-scaleproductionofpharmaceuticalproteinsinplantcellculture—theprotalixexperienceYoramTekoah*,AvidorShulman,TaliKizhner,IlyaRuderfer,LiatFux,YakirNataf,DanielBartfeld
2、,TamiAriel,SvetlanaGingis–Velitski,UriHananiaandYosephShaaltielProtalixBiotherapeutics,Carmiel,IsraelReceived17March2015;Summaryrevised14May2015;ProtalixBiotherapeuticsdevelopsrecombinanthumanproteinsandproducestheminplantcellaccepted26May2015.cultur
3、e.Taliglucerasealfahasbeenthefirstbiotherapeuticexpressedinplantcellstobe*Correspondence(Tel97289028100;approvedbyregulatoryauthoritiesaroundtheworld.Othertherapeuticproteinsarebeingfax:97289981034;developedandarecurrentlyatvariousstagesofthepipeline.
4、Thisreviewsummarizesthemajoremailyoram.tekoah@protalix.com)milestonesreachedbyProtalixBiotherapeuticstoenablethedevelopmentofthesebiothera-peutics,includingplatformestablishment,celllineselection,manufacturingprocessandgoodmanufacturingpracticeprinci
5、plestoconsiderfortheprocess.ExamplesofthevariousproductsKeywords:b-glucocerebrosidase,currentlybeingdevelopedarealsopresented.enzymereplacementtherapy,molecularfarming,oraldelivery,plantcellculture,ProtalixBiotherapeutics.suchasthoserelatedtobovinesp
6、ongiformencephalopathy,Introductionplantcellsystemsnaturallydonotcarrytheriskofinfectionby,Theuseofplantcellculturesfortheproductionofhumanortransmissionof,humanorotheranimalpathogens.More-biopharmaceuticalproteinshasbeenunderevaluationforover,plantc
7、ellculturespresentanaturalbarriertomammaliandecades(Sijmonsetal.,1990).Plantcellculturesofferseveralpathogencontamination,asattemptstopropagatemammalianmajoradvantagesovermammaliancellcultures,includingcost-virusesinplantcellshavebeenunsuccessful(EMA
8、,2013).Planteffectivenessandpotentlackofanymammalian-derivedcom-virusescannotspreadoutinplantcellculturesastheylacktheponentsintheproductionprocess(Hellwigetal.,2004).Inrouteofvirusmovement,thatisplasmodesmata(Raffaeleaddition,theyenableprecisecontro