ArticleRNACircularizationDiminishesImmunogenicityandCanExtendTranslationDurationInVivoGraphicalAbstractHighlightsdTriphosphorylatedandlinearRNAcontaminantsprovokeinnateimmuneresponsesdPurifiedexogenouscircRNAdoesnottriggerRIG-IdcircRNAdoesnottriggerTLRsinoverexpressioncelllinesdNanoformulatedcircRNAistranslatedinmousetissuesAuthorsR.AlexanderWesselhoeft,PiotrS.Kowalski,FrancesC.Parker-Hale,YuxuanHuang,NamitaBisaria,DanielG.AndersonCorrespondencedgander@mit.eduInBriefWesselhoeftetal.findthatexogenouscircularRNAsareabletobypassRNAsensors,therebyavoidingantiviraldefenseinductionuponcellularentry.Theyreportthatnanoformulated,syntheticprotein-codingcircRNAcanbetranslatedinmousetissues,providingevidenceforthepotentialofcircRNAasavectorfortherapeuticgeneexpression.Wesselhoeftetal.,2019,MolecularCell74,1–13May2,2019ª2019ElsevierInc.https://doi.org/10.1016/j.molcel.2019.02.015MolecularCellArticleRNACircularizationDiminishesImmunogenicityandCanExtendTranslationDurationInVivoR.AlexanderWesselhoeft,1,2PiotrS.Kowalski,1,3FrancesC.Parker-Hale,2,4YuxuanHuang,1NamitaBisaria,5andDanielG.Anderson1,3,6,7,8,*1DavidH.KochInstituteforIntegrativeCancerResearch,MassachusettsInstituteofTechnology,Cambridge,MA02142,USA2DepartmentofBiology,MassachusettsInstituteofTechnology,Cambridge,MA02142,USA3DepartmentofChemicalEngineering,MassachusettsInstituteofTechnology,Cambridge,MA02142,USA4DepartmentofPoliticalScience,MassachusettsInstituteofTechnology,Cambridge,MA02142,USA5WhiteheadInstituteforBiomedicalResearch,Cambridge,MA02142,USA6InstituteforMedicalEngineeringandScience,MassachusettsInstituteofTechnology,Cambridge,MA02142,USA7HarvardandMITDivisionofHealthScienceandTechnology,MassachusettsInstituteofTechnology,Cambridge,MA02142,USA8LeadContact*Correspondence:dgander@mit.eduhttps://doi.org/10.1016/j.molcel.2019.02.015SUMMARYCircularRNAs(circRNAs)areaclassofsingle-strandedRNAswithacontiguousstructurethathaveenhancedstabilityandalackofendmotifsnecessaryforinteractionwithvariouscellularpro-tein...
