Cell-Selective Therapies for Coronary Artery Disease
冠状动脉疾病的细胞选择性疗法
基本信息
- 批准号:10543849
- 负责人:
- 金额:$ 48.6万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-07-15 至 2025-12-31
- 项目状态:未结题
- 来源:
- 关键词:Adenovirus VectorAffectAnimal ModelApolipoprotein EArterial Fatty StreakAtherosclerosisBiologicalBlood VesselsCannulationsCardiovascular DiseasesCardiovascular systemCarotid ArteriesCategoriesCause of DeathCell physiologyCellsCessation of lifeClinicalClinical ResearchCoronary ArteriosclerosisCoronary arteryCyclin-Dependent Kinase InhibitorDevelopmentEndothelial CellsEndotheliumEpidemicEventExhibitsFoundationsFunctional disorderGoalsHeartHumanHyperplasiaIncidenceInfectionInflammationInflammatory InfiltrateInjuryInterleukin-1 betaInterventionKnock-outLipidsMessenger RNAMicroRNAsModelingMusOryctolagus cuniculusPenetrationPeptidesPharmaceutical PreparationsPhysiologyProteinsRattusRecurrenceRegional PerfusionResistanceSafetySiteSmall Interfering RNASmooth Muscle MyocytesTechnologyTestingTherapeuticThrombophiliaThrombosisTimeToxic effectTranslatingUntranslated RegionsVascular Endothelial CellVascular Smooth MuscleVenouscyclin-dependent kinase inhibitor 1Bdesigndisabilityefficacy evaluationendonucleaseex vivo perfusionfemoral arteryhealinghuman tissuemouse modelnanoparticlenanoswitchnanotherapeuticnanotherapynovelnovel strategiesoverexpressionpersonalized medicinepharmacologicpreclinical studyprotein expressionrecombinant virusresponserestenosisself assemblytooltranslational potentialtreatment strategyuptakevascular smooth muscle cell proliferation
项目摘要
Atherosclerotic cardiovascular disease (CVD) represents a serious affliction affecting millions globally. Despite
recent advances in pharmacological and percutaneous interventions, CVD remains the leading cause of death
and disability in the world. One of the main therapeutic challenges facing atherosclerotic CVD is the delivery of
therapies to the atherosclerotic plaque that target the specific cells which contribute to its formation, while
protecting the endothelium. Vascular endothelial cells provide crucial protection against lipid uptake,
inflammation and thrombosis. We hypothesize that cell-selective therapy that inhibits infiltration of inflammatory
cells and proliferation of vascular smooth muscle cells, while protecting endothelia cell function will be effective
in combating CVD and thrombosis. To achieve this goal, we will develop a novel miRNA switch that combines
synthetically modified mRNA with miRNA target site. As a delivery platform we will utilize the cationic amphipathic
cell-penetrating peptide that forms a self-assembled, compacted, nanoparticle when mixed with synthetic mRNA.
Moreover, to increase the targeting of inflammation in the atherosclerotic plaque, we will combine the miRNA
switch together with siRNA targeting IL1-β to generate nanoparticles using the same cationic amphipathic cell-
penetrating peptide. In two specific aims, we will test 1) the efficacy of this cell-selective nanotherapy to inhibit
atherosclerosis and restenosis after percutaneous intervention, while protecting EC to reduce thrombosis; and
2) the translational potential of the miRNA switch nanotherapy in viable, isolated human coronary arteries.
Completion of the aims will provide the foundation for the development of a novel category of biological drugs
that can accommodate the advent of personalized medicine and will advance the treatment of cardiovascular
disease.
动脉粥样硬化性心血管疾病(CVD)是一种严重的疾病,影响着全球数百万人。尽管
药物和经皮干预的最新进展,CVD 仍然是死亡的主要原因
和世界上的残疾。动脉粥样硬化性 CVD 面临的主要治疗挑战之一是提供
针对动脉粥样硬化斑块的治疗,针对有助于其形成的特定细胞,同时
保护内皮。血管内皮细胞提供重要的保护,防止脂质摄取,
炎症和血栓形成。我们假设抑制炎症浸润的细胞选择性疗法
细胞和血管平滑肌细胞的增殖,同时保护内皮细胞功能将有效
对抗心血管疾病和血栓形成。为了实现这一目标,我们将开发一种新颖的 miRNA 开关,它将
具有 miRNA 靶位点的合成修饰 mRNA。作为递送平台,我们将利用阳离子两亲性
细胞穿透肽,与合成 mRNA 混合时形成自组装、压缩的纳米颗粒。
此外,为了增加动脉粥样硬化斑块中炎症的靶向性,我们将结合 miRNA
与靶向 IL1-β 的 siRNA 一起切换,使用相同的阳离子两亲细胞生成纳米颗粒 -
穿透肽。为了实现两个具体目标,我们将测试 1) 这种细胞选择性纳米疗法抑制
经皮介入治疗后动脉粥样硬化和再狭窄,同时保护EC减少血栓形成;和
2) miRNA 开关纳米疗法在活的、分离的人类冠状动脉中的转化潜力。
目标的完成将为新型生物药的开发奠定基础
可以适应个性化医疗的出现,并将促进心血管疾病的治疗
疾病。
项目成果
期刊论文数量(0)
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会议论文数量(0)
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Hana Totary-Jain其他文献
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{{ truncateString('Hana Totary-Jain', 18)}}的其他基金
MicroRNA-Based, Cell-Selective Therapy for Coronary Artery Disease
基于 MicroRNA 的冠状动脉疾病细胞选择性疗法
- 批准号:
9474655 - 财政年份:2015
- 资助金额:
$ 48.6万 - 项目类别:
Cell-Selective Therapies for Coronary Artery Disease
冠状动脉疾病的细胞选择性疗法
- 批准号:
10323294 - 财政年份:2015
- 资助金额:
$ 48.6万 - 项目类别:
MicroRNA-Based, Cell-Selective Therapy for Coronary Artery Disease
基于 MicroRNA 的冠状动脉疾病细胞选择性疗法
- 批准号:
9268806 - 财政年份:2015
- 资助金额:
$ 48.6万 - 项目类别:
MicroRNA-Based, Cell-Selective Therapy for Coronary Artery Disease
基于 MicroRNA 的冠状动脉疾病细胞选择性疗法
- 批准号:
9110298 - 财政年份:2015
- 资助金额:
$ 48.6万 - 项目类别:
MicroRNA Detargeting Novel Therapy for Coronary Artery Disease
MicroRNA 脱靶治疗冠状动脉疾病的新疗法
- 批准号:
8838234 - 财政年份:2013
- 资助金额:
$ 48.6万 - 项目类别:
MicroRNA Detargeting Novel Therapy for Coronary Artery Disease
MicroRNA 脱靶治疗冠状动脉疾病的新疗法
- 批准号:
8788329 - 财政年份:2013
- 资助金额:
$ 48.6万 - 项目类别:
MicroRNA Detargeting Novel Therapy for Coronary Artery Disease
MicroRNA 脱靶治疗冠状动脉疾病的新疗法
- 批准号:
8306029 - 财政年份:2011
- 资助金额:
$ 48.6万 - 项目类别:
Regulation of Vascular Smooth Muscle Cell Proliferation
血管平滑肌细胞增殖的调节
- 批准号:
7406304 - 财政年份:2008
- 资助金额:
$ 48.6万 - 项目类别:
Regulation of Vascular Smooth Muscle Cell Proliferation
血管平滑肌细胞增殖的调节
- 批准号:
7587450 - 财政年份:2008
- 资助金额:
$ 48.6万 - 项目类别:
Regulation of Vascular Smooth Muscle Cell Proliferation
血管平滑肌细胞增殖的调节
- 批准号:
7816769 - 财政年份:2008
- 资助金额:
$ 48.6万 - 项目类别:
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