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1、RNAVIRUSVECTORS:GENETRANSFERANDGENEEXPRESSIONThetransductionefficiencyofthesevectorsrangedfrom58-97%extensivecelldeath.TheseresultsshowthatthemousehepatitisinCEMcells.Aftersorting,thetransducedcellswereallgreatercoronavirus,normallynotcapableofinfectinghumancells,canbethan
2、90%GFPpositive.InthemorerobustHIVinfectedsupernatantgeneticallyredirectedviabispecificadapterstoaspecificreceptorre-challengeassay,CEMcellswereinfectedfromtheprimarycultureexpressedonhumancancercells,consequentlyleadingtorapidcellsupernatantusingequalamountsofp24antigen.Th
3、reelentiviraldeath.Thisresultprovidesinterestingleadsforfurtherinvestigationsvector-expressedanti-VifsiRNAs(VifA,VifBandVifC)celllinesontheuseofcoronavirusesasanti-tumoragents.wereactiveagainstHIV-1showinggreaterthan90%inhibitionofviralreplication.VifAwasthemosteffectivesh
4、owinggreaterthen510.TheEffectofGlobinLocusControlRegionlogsreductionofviraloutput.ImportantlyVifAgave100%inhibition(LCR)ElementsortheMSCV-LTRonPromoterofHIVgenomicRNAandHIVcDNA,confirmingtheactivityofTrappingbyIntegratedLentiviralVectorGenomesthissiRNAtowardsincomingviralg
5、enomicRNA.ConverselyVifBByoungY.Ryu,DerekA.Persons,ArthurW.Nienhuis.andVifCshowednoinhibitionofHIVRNAandcDNA.Inpost1Hematology/Oncology,St.JudeChildren’sResearchHospital,infection,VifAexhibitedatransientreductionofp24expressionMemphis,TN.whileVifBandVifCshowedlimitedeffect
6、sonHIVp24.Mostimportantly,allthreeanti-VifsiRNAsyieldeddefectiveviralparticlesIntegratingvectorsaredesirableforgenetherapyofinheritedresultinginapotentlossofinfectivity,presumablyaresultoflossblooddisorderstoachievepermanentgeneticmodificationandstableofVifandsubsequentinc
7、orporationoftheAPOBEC3Gcytidineexpressionoftransgenesinhematopoieticcells.However,threedeaminaseintothevirionsandsubsequentlymutatestheviralDNApatientswithseverecombinedimmunodeficiencyenrolledinageneintonon-infectivity.therapytrialofaretroviralvectordevelopedleukemiaandac
8、tivationTheseresultsclearlydemonstratethatthelentiviral-basedvectorsoftheLMO2proto-oncoge
