Exosomes in Cancer Therapy
外泌体在癌症治疗中的应用
基本信息
- 批准号:9897907
- 负责人:
- 金额:$ 4.02万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-12-27 至 2021-11-30
- 项目状态:已结题
- 来源:
- 关键词:ApoptosisApplications GrantsBiological AssayBiologyBlood CirculationBrainCD47 geneCell ProliferationCellsClinicClinicalCodon NucleotidesComplementCoupledCultured CellsDNADataDiseaseEatingElectroporationEndopeptidase KEngineeringExhibitsExtracellular ProteinFibroblastsFrequenciesFutureGeneticGenetic studyGenetically Engineered MouseGlycineHalf-LifeHumanITGAM geneImageImpairmentIntegrinsInvestigationKRAS2 geneLiposomesLiverLungMalignant NeoplasmsMalignant neoplasm of pancreasMediatingMediator of activation proteinMolecularMusMutationOncogenicPancreasPancreatic Ductal AdenocarcinomaPathogenesisPathway interactionsPatientsPerformancePhagocytesPharmaceutical PreparationsPharmacologyPhysiologicalPlayProcessProteinsProteomicsRNARNA InterferenceResearchRoleRouteSignal TransductionSmall Interfering RNASurvival RateSystemTechniquesTertiary Protein StructureTestingTherapeuticTissuesTrypsinWestern BlottingXenograft procedurebasecancer therapydesigndosageeffective therapyexosomeexperimental studyextracellular vesiclesimaging modalityimprovedinsightknowledge translationmacrophagemonocytemouse modelnanoparticleneutralizing antibodynovel strategiesnovel therapeuticsoff-label useoutcome forecastpancreatic cancer cellspancreatic cancer modelpancreatic neoplasmpenis foreskinpre-clinicalpreclinical studyprogramssmall hairpin RNAstandard of caretherapeutic evaluationtumortumor progression
项目摘要
Project Summary
Pancreatic Ductal Adenocarcinoma (PDAC) has a dismal prognosis with a median survival of about 6 months
for patients with metastatic disease despite the use of current treatments. Therefore, PDAC is in urgent need
of effective therapies. About 80% of PDAC patients exhibit mutation in KRAS, with substitution of a glycine
residue at codon 12, such as KRASG12D, observed in high frequency. Many studies in mice unequivocally show
that direct inhibition oncogenic KRAS significantly suppresses tumor progression. Despite such compelling
evidence for the functional role of oncogenic KRAS in the PDAC pathogenesis, direct targeting of oncogenic
KRAS has been elusive and it has often been dubbed as ‘undruggable’. In this grant application, we propose to
explore a novel approach to target oncogenic KRAS using physiological nanoparticles known as exosomes.
Exosomes are 40-150 nm extracellular vesicles (EVs) that contain DNA, RNA and proteins, and can deliver
their contents efficiently into cells they fuse with and/or enter. Exploiting this unique feature of exosomes, our
research team proposes in this grant application to test the central hypothesis that ‘exosomes can be
engineered to deliver RNA interference (RNAi) molecules to target KRASG12D in pancreatic cancer’.
Successful completion of the proposed studies will determine whether exosomes exhibit a superior ability to
deliver RNAi molecules for the treatment of pancreatic cancer when compared to liposomes. Additionally, after
such increased ability is investigated using multiple experimental systems, the proposal will further identify
mechanism/s associated with the enhanced efficacy of exosomes in the delivery of RNAi molecules.
Collectively, the proposal is designed to enable in-depth pre-clinical studies coupled with an investigation into
the unique mechanism of action of exosomes to potentially facilitate future therapeutic testing in patients with
PDAC.
项目摘要
胰腺导管腺癌(PDAC)预后差,中位生存期约为6个月
对于转移性疾病的患者,尽管使用当前的治疗。因此,PDAC是迫切需要的
有效的治疗方法。约80%的PDAC患者表现出KRAS突变,其中甘氨酸取代
在密码子12的残基,如KRASG 12 D,观察到的频率很高。许多对老鼠的研究明确表明
直接抑制致癌KRAS可显著抑制肿瘤进展。尽管如此引人注目
致癌KRAS在PDAC发病机制中的功能作用的证据,直接靶向致癌KRAS,
KRAS一直难以捉摸,它经常被称为“坚不可摧”。在这项拨款申请中,我们建议
探索一种新的方法,使用称为外泌体的生理纳米颗粒靶向致癌KRAS。
外来体是40-150 nm的细胞外囊泡(EV),其含有DNA、RNA和蛋白质,并且可以递送DNA、RNA和蛋白质。
它们的内容物有效地进入它们与之融合和/或进入的细胞。利用外泌体的这一独特功能,
一个研究小组在这项拨款申请中提出了一个中心假设,即“外泌体可以被
工程化以递送RNA干扰(RNAi)分子以靶向胰腺癌中的KRASG 12 D。
成功完成拟议的研究将确定外泌体是否表现出上级能力,
当与脂质体相比时,递送RNAi分子用于治疗胰腺癌。此外,在
使用多个实验系统研究这种增加的能力,该提案将进一步确定
在RNAi分子的递送中与外泌体的增强功效相关的一种或多种机制。
总的来说,该提案旨在进行深入的临床前研究,并调查
外泌体的独特作用机制可能有助于未来在患有
PDAC。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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{{ truncateString('RAGHU KALLURI', 18)}}的其他基金
Mechanisms associated with organotropic metastasis
与器官转移相关的机制
- 批准号:
10295926 - 财政年份:2021
- 资助金额:
$ 4.02万 - 项目类别:
Mechanisms associated with organotropic metastasis
与器官转移相关的机制
- 批准号:
10439900 - 财政年份:2021
- 资助金额:
$ 4.02万 - 项目类别:
Mechanisms associated with organotropic metastasis
与器官转移相关的机制
- 批准号:
10532826 - 财政年份:2021
- 资助金额:
$ 4.02万 - 项目类别:
Employing mouse models to translate early detection of pancreas cancer
利用小鼠模型转化胰腺癌的早期检测
- 批准号:
8904197 - 财政年份:2015
- 资助金额:
$ 4.02万 - 项目类别:
Employing mouse models to translate early detection of pancreas cancer
利用小鼠模型转化胰腺癌的早期检测
- 批准号:
9097660 - 财政年份:2015
- 资助金额:
$ 4.02万 - 项目类别: