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(23)今日发布03篇（共计55篇）CurrHeartFailRepEarlyRecent,Nov28,今日发布01篇EurJPrevCardiolDec01,:26(18)今日发布21篇CirculationEarlyRecent,Nov29,今日发布02篇RECOMMEND推荐阅读01AAV-CRISPR/Cas9介导的基因编辑对家族性高胆固醇血症动脉粥样硬化的改善作用Circulationresearch-articleHuanZhao,YanLi,etc.1小时前等19用户推荐阅读本文Background:Mutationsinlow-densitylipoproteinreceptor(LDLR)areoneofthemaincausesoffamilialhypercholesterolemia(FH),whichinducesatherosclerosisandhasahighlifetimeriskofcardiovasculardisease.Theclusteredregularlyinterspacedshortpalindromicrepeats(CRISPR)/Cas9systemisaneffectivetoolforgeneeditingtocorrectgenemutationsandthusamelioratedisease.低密度脂蛋白受体（LDLR）基因突变是家族性高胆固醇血症（FH）的主要病因之一，它可导致动脉粥样硬化，并具有心血管疾病的高风险。聚类规则间隔短回文重复序列（CRISPR）/Cas9系统是一种有效的基因编辑工具，可以纠正基因突变，从而改善疾病。Methods
odeterminewhetherinvivosomaticcellgeneeditingthroughtheCRISPR/Cas9systemdeliveredbyadeno-associatedvirus(AAV)couldtreatFHcausedbytheLdlrmutantinamousemodel.Wegeneratedanonsensepointmutationmouseline,LdlrEX,basedonarelevantFH-relatedgenemutation.TheAAV-CRISPR/Cas9wasdesignedtocorrectthepointmutationintheLdlrgeneinhepatocytesandwasdeliveredsubcutaneouslyintoLdlrEXmice.目的探讨腺相关病毒（AAV）介导的CRISPR/Cas9系统体内体细胞基因编辑能否治疗Ldlr突变体引起的FH。我们根据一个相关的FH相关基因突变产生了一个无义点突变小鼠系LdlrEX。AAV-CRISPR/Cas9被设计用于纠正肝细胞Ldlr基因的点突变，并被皮下注射到LdlrEX小鼠体内。Results:WefoundthathomogeneousLdlrEXmice(n=6)exhibitedsevereatheroscleroticphenotypesafteraHigh-fatdietregimenandtheLdlrmutationwascorrectedinasubsetofhepatocytesafterAAV-CRISPR/Cas9treatment,withLDLRproteinexpressionpartiallyrestored(n=6).Comparedwiththecontrolgroups(n=6eachgroup),theAAV-CRISPR/Cas9withtargetedsgRNAgroup(n=6)hadsignificantreductionsintotalcholesterol,totaltriglyceride,andLDL-cholesterolintheserum,whiletheaortahadsmalleratheroscleroticplaquesandalowerdegreeofmacrophageinfiltration.我们发现，在高脂饮食方案后，同质LdlrEX小鼠（n=6）表现出严重的动脉粥样硬化表型，AAV-CRISPR/Cas9治疗后，肝细胞亚群中的Ldlr突变得到纠正，Ldlr蛋白表达部分恢复（n=6）。与对照组（每组6例）相比，靶向sgRNA组（每组6例）的AAV-CRISPR/Cas9能显著降低血清总胆固醇、总甘油三酯和低密度脂蛋白胆固醇，而主动脉粥样斑块较小，巨噬细胞浸润程度较低。Conclusions:OurworkshowsthatinvivoAAV-CRISPR/Cas9-mediatedLdlrgenecorrectioncanpartiallyrescueLDLRexpressionandeffectivelyameliorateatherosclerosisphenotypesinLdlrmutants,providingapotentialtherapeuticapproachforthetreatmentofFHpatients.我们的研究表明，体内AAV-CRISPR/Cas9介导的Ldlr基因修饰可以部分挽救Ldlr的表达，有效改善Ldlr突变体的动脉粥样硬化表型，为FH患者的治疗提供了一种潜在的治疗途径。扫描
