Efficient inhibition of miR-155 function in vivo by peptide nucleic acids

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1、4466–4475NucleicAcidsResearch,2010,Vol.38,No.13Publishedonline11March2010doi:10.1093/nar/gkq160EfficientinhibitionofmiR-155functioninvivobypeptidenucleicacids1,213MartinM.Fabani*,CeiAbreu-Goodger,DonnaWilliams,PaulA.Lyons,1321AdrianG.Torres,KennethG.C.Smith,A

2、ntonJ.Enright,MichaelJ.Gaitand4,ElenaVigorito*12MedicalResearchCouncil,LaboratoryofMolecularBiology,CambridgeCB20QH,EuropeanMolecularBiologyLaboratory,EuropeanBioinformaticsInstitute,WellcomeTrustGenomeCampus,CambridgeCB1031SD,CambridgeInstituteforMedicalRese

3、arch,UniversityofCambridge,CambridgeCB20XYand4LaboratoryofLymphocyteSignallingandDevelopment,BabrahamInstitute,BabrahamResearchCampus,CambridgeCB223AT,UKReceivedJanuary18,2010;RevisedandAcceptedFebruary24,2010ABSTRACTregionsontheirtargetmRNAs,theymediategenes

4、ilencingbytranslationalrepression,mRNAdegradationMicroRNAs(miRNAs)playanimportantroleinorboth(2).MiRNAsregulateawidevarietyofbiologicalDownloadedfromdiversephysiologicalprocessesandarepotentialprocessessuchasproliferation,differentiation,cellularmi-therapeutic

5、agents.Syntheticoligonucleotidesgration,cellfatedeterminationandapoptosis.Notsur-(ONs)ofdifferentchemistrieshaveprovensuccess-prisingly,deregulationofmiRNAexpressionhasbeenfulforblockingmiRNAexpression.However,theirlinkedtohumandiseasessuchascancerandautoimmu

6、nenar.oxfordjournals.orgspecificityandefficiencyhavenotbeenfullydysfunction.OneofthefirstmiRNAsidentifiedwithevaluated.Here,weshowthatpeptidenucleiconcogenicpotentialwasmiR-155.Encodedwithinanacids(PNAs)efficientlyblockakeyinducibleexonofthenon-codingRNABIC,miR

7、-155isderegulatedmiRNAexpressedinthehaematopoieticsystem,inanumberofdifferenthumancancers,mostofwhichareatsibcbonOctober10,2011ofB-cellorigin(3–6).Moreover,miR-155over-expressionmiR-155,inculturedBcellsaswellasinmice.duringB-celldevelopmentissufficienttotriggerB

8、-cellRemarkably,miR-155inhibitionbyPNAinprimarytransformation(7).HighlevelsofmiR-155arenotBcellswasachievedintheabsenceofanytrans-restrictedtotransformedcells.Inthecourseofanfectionagent.