1EwartDT,etal.AnnRheumDis2018;0:1–10.doi:10.1136/annrheumdis-2018-213454ReviewGeneeditingforinflammatorydisordersDavidTEwart,1ErikJPeterson,1CliffordJSteer2,3AbstRActTechnologyforpreciseandefficientgeneticeditingisconstantlyevolvingandisnowcapableofhumanclinicalapplications.Autoimmuneandinflammatorydiseasesarechronic,disabling,sometimeslife-threatening,conditionsthatfeatureheritablecomponents.Bothprimarygeneticlesionsandtheinflammatorypathobiologyunderlyingthesediseasesrepresentfertilesoilfornewtherapiesbasedonthecapabilitiesofgeneediting.Theabilitytoorchestrateprecisetargetedmodificationstothegenomewilllikelyenablecell-basedtherapiesforinflammatorydiseasessuchasmonogenicautoinflammatorydisease,acquiredautoimmunediseaseandforregenerativemedicineinthesettingofaninflammatoryenvironment.Here,wediscussrecentadvancesingenomeeditingandtheirevolvingapplicationsinimmunoinflammatorydiseases.StrengthsandlimitationsofoldergeneticmodificationtoolsarecomparedwithCRISPR/Cas9,baseediting,RNAediting,targetedactivatorsandrepressorsoftranscriptionandtargetedepigeneticmodifiers.Commonlyemployeddeliveryvehiclestotargetcellsortissuesofinterestwithgeneticmodificationmachinery,includingviral,non-viralandcellularvectors,aredescribed.Finally,applicationsinanimalandhumanmodelsofinflammatorydiseasesarediscussed.UseofchimericautoantigenreceptorTcells,correctionofmonogenicdiseaseswithgeneticallyeditedhaematopoieticstemandprogenitorcells,engineeringofinducedpluripotentstemcellsandexvivoexpansionandmodificationofregulatoryTcellsforarangeofchronicinflammatorydiseasesarereviewed.IntRoductIonManychronichumanautoimmuneandautoinflam-matorydiseasesrequireindefinitetherapy.Despitemajordevelopmentsinmolecularmechanism-fo-cusedtherapyforrheumaticconditionsinthepastseveraldecades,substantialmorbidityandmortalitystillattendsthesediseases.Emerginggenetherapyapproachesofferthepromiseofmorespecificanddurabletreatmentsthatmaycircumventtoxicitiesoftraditionalmedicalmanagementforinflamma-torydisease.Rareperio...
