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ID:33547436
大小:1.95 MB
页数:35页
时间:2019-02-27
《vegf启动子驱动双自杀基因靶向治疗大肠癌的实验研究》由会员上传分享,免费在线阅读,更多相关内容在学术论文-天天文库。
1、ABSTRACTtotumorcellsbyvectorsandexpressedselectivityinthetulllorcells;oncesufficientlevelsofenzymearepresentinthetransducedcells,aprodrugisadministered,thisisthesecondstep,theenzymeconvexnon—cytotoxicprodrugstocytotoxicdrugsSOastokillcancercells.Thusakeycomponentofsuici
2、degenetherapyisthatthesuicidegeneneedstobeexpressedselectivityandefficientlyintumorcellsinordertosparenormaltissuefromdamage.AlthoughpreviousattemptstotargetsuicidegenetherapytoCRCusingthecarcinoembryonicantigen(CEA)promoterhavedemons仃atedspecificity,thishasbeenachieved
3、atthecostof10··to300·-foldlossinactivitycompared谢mstrongbutnonspecificroussarcomavirus(RSV)orcytomegalovirus(CMV)promoters;What’SmoregenetherapyofCRCusingsuicidegenedrivenbyCEApromoterisnotadaptedtotumorswitlllowexpressionlevelofCEA.Recentyearstherapiesthattargettumorbl
4、oodvesselsattractmoreandmorepeople’Sattention.ManystudieshavefoundthatVEGFoverexpressinmanysolidtumorcells,butexpresslittleornotatallinnormalcells.AtthesametimetheexpressionofVEGFislinkedwitllthetumor’smalignance.SoweconstructtheadenoviruscontainingCDglyTKfusiongenedriv
5、enbyVEGFpromoter(AdVEGF-CDglyTK)anditWastransfectedintoCRCcelllineLovo.Agenetherapyvectorhastomeetseveralconditions:1.safety,whichCanbebetterachieved、析tllanonintegrativeveetogasitavoidstheriskforinsertionalmutagenesis;2.abilitytobeeasilyandinexpensivelyproducedatalarge-
6、scaleinthelaboratory;3.stabilityintargetcells,whichisfavoredwithlow-immunogenicvectors;4.highcapacityallowingthepossibilityofintroducingfull—lengthDNAsequencesformostgenes,longfull—lengthcDNAs,endogenouspromotersoradditionalregulatorysequencessuchasenhancersorinsulators
7、,whichcarlprovideatightlyregulatedexpressionofthetherapeuticgene,similartophysiologicconditions.Adenovirusesseemtoaccomplishmostoftheseconditionsastheyarenotintegrative,theyhaveacapacityof36kb,theyCanbe硕士学位论文easilyproducedathightitersinthelaboratoryandCanbedeliveredtoal
8、argemassofcells.That’Swhyweselecttheadenovirusasthevectorsforsuicidegenetherapy.Ourpreviousstudiesfoundthatthe
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