ArticleInVivoTargetGeneActivationviaCRISPR/Cas9-MediatedTrans-epigeneticModulationGraphicalAbstractHighlightsdACRISPR/Cas9systemtranscriptionallyactivatesendogenoustargetgenesinvivodRecruitingthetranscriptionalmachineryinducestrans-epigeneticremodelingdInducingtargetgeneexpressionleadstophysiologicalphenotypesinpostnatalmammalsdThesystemamelioratessymptomsassociatedwithseveralmousemodelsofhumandiseasesAuthorsHsin-KaiLiao,FumiyukiHatanaka,ToshikazuAraoka,...,Li-FanLu,ConcepcionRodriguezEsteban,JuanCarlosIzpisuaBelmonteCorrespondencebelmonte@salk.eduInBriefInvivodeliveryofaCas9-basedepigeneticgeneactivationsystemamelioratesdiseasephenotypesinmousemodelsoftypeIdiabetes,acutekidneyinjury,andmusculardystrophyLiaoetal.,2017,Cell171,1495–1507December14,2017ª2017ElsevierInc.https://doi.org/10.1016/j.cell.2017.10.025ArticleInVivoTargetGeneActivationviaCRISPR/Cas9-MediatedTrans-epigeneticModulationHsin-KaiLiao,1,7FumiyukiHatanaka,1,7ToshikazuAraoka,1,2,7PradeepReddy,1Min-ZuWu,1,2YinghuiSui,3TakayoshiYamauchi,1,2MasahiroSakurai,1DavidD.O’Keefe,1EstrellaNu´n˜ez-Delicado,2PedroGuillen,4JosepM.Campistol,5Cheng-JangWu,6Li-FanLu,6ConcepcionRodriguezEsteban,1andJuanCarlosIzpisuaBelmonte1,8,*1GeneExpressionLaboratory,SalkInstituteforBiologicalStudies,LaJolla,CA92037,USA2UniversidadCatolica,SanAntoniodeMurcia,CampusdelosJeronimos,135,30107Guadalupe,Spain3DepartmentofPediatricsandCellularandMolecularMedicine,UniversityofCalifornia,SanDiego,LaJolla,CA92093,USA4FundacionPedroGuillen,ClinicaCEMTRO,AvenidaVentisquerodelaCondesa,42,28035Madrid,Spain5HospitalClinicofBarcelona,CarrerVillarroel,170,08036Barcelona,Spain6DivisionofBiologicalSciences,UniversityofCalifornia,SanDiego,LaJolla,CA92037,USA7Theseauthorscontributedequally8LeadContact*Correspondence:belmonte@salk.eduhttps://doi.org/10.1016/j.cell.2017.10.025SUMMARYCurrentgenome-editingsystemsgenerallyrelyoninducingDNAdouble-strandbreaks(DSBs).Thismaylimittheirutilityinclinicaltherapies,asun-wantedmutationscausedbyDSBscanhavedelet...
