42‐ and 63‐bp anti‐MDR1‐siRNAs bearing 2′‐OMe modifications in nuclease‐sensitive sites induce specific and potent gene silencing

摘要

DsRNAslongerthan30bpinduceinterferonresponseandglobalchangesingeneexpressionprofileinmammalians.21bpsiRNAand25/27bpdsiRNAactingviaRNAinterferencemechanismareusedforspecificgenesilencinginthisclassoforganisms.Wedesignedselectively2′‐O‐methyl‐modified42and63bpanti‐MDR1‐siRNAsthatsilencetheexpressionofP‐glycoproteinandrestorethesensitivityofdrug‐resistantcancercellstocytostaticmoreefficientlythancanonical21bpsiRNAs.WealsoshowthattheyactinaDicer‐independentmodeandaredevoidofimmunostimulatingproperties.Ourfindingssuggestthat42and63bpsiRNAscouldbeusedaspotentialtherapeutics...