Daily Quantification of Cancer-Associated Exosomal miRNA in Patient Blood by Photonic Crystal-Enhanced Quantum Dot Emission
通过光子晶体增强量子点发射对患者血液中癌症相关外泌体 miRNA 进行每日定量
基本信息
- 批准号:9899743
- 负责人:
- 金额:$ 37.64万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-03-19 至 2023-02-28
- 项目状态:已结题
- 来源:
- 关键词:AcetatesAdoptionAffectAftercareAwardBiological AssayBiological MarkersBiometryBloodBlood specimenCancer PatientClinicalClinical DataClinical OncologyClinical TrialsClosure by clampCollectionCouplingCrystallizationDetectionDevicesDiagnosisDiseaseDropsEffectivenessElectronicsEngineeringEnrollmentEpidemiologistEpidemiologyEquilibriumEquipmentGeneticGoalsGrowthHome environmentHumanIndividualInstitutional Review BoardsInterventionKnowledgeLabelLaboratoriesLengthLightMalignant NeoplasmsMeasurementMeasuresMetastatic Prostate CancerMethodsMicroRNAsMicroscopeMolecularMolecular ProfilingMonitorNucleic AcidsOncologistOpticsOutcomePathologistPatient-Focused OutcomesPatientsPeptide Nucleic AcidsPharmacotherapyPrednisonePrognostic MarkerProspective StudiesQuantum DotsRegimenReproducibilityResearch PersonnelReverse Transcriptase Polymerase Chain ReactionSamplingScreening for cancerSeriesSignal TransductionSpecificitySpecimenSpottingsSurfaceTechnologyTemperatureTherapeuticTimeTrainingTranslationsTreatment EfficacyTreatment outcomeVariantWorkabirateroneadvanced prostate cancerassay developmentbasebiomarker discoverycancer biomarkerscancer survivalcastration resistant prostate cancercharge coupled device camerachemotherapyclinical applicationclinical diagnosticscostdensitydesigndigitaldocetaxeldrug efficacyelectric fieldindividual patientinsightinstrumentinterestmolecular imagingnanoprobenew technologynovelphotonicsportabilitypredicting responsepredictive markerprospectiverapid techniqueratiometricresponseroutine screeningsingle moleculestandard of caresuccesstumortumor heterogeneity
项目摘要
ABSTRACT
The primary goal of this proposal is to develop a new technology that can allow patients to repeatedly measure
nucleic acid-based cancer biomarkers from a single drop of blood on a daily basis. This assay is being developed
for specific clinical applications to determine drug treatment efficacies, prognosticate survival, and monitor post-
treatment intervention by evaluating candidate nucleic acids shed from the tumor into blood of a cancer patient.
We are focusing on detecting microRNA due to a very strong correlation with survival that our team has recently
identified for patients with metastatic prostate cancer. We hypothesize that by measuring the concentrations of
these markers in patients on a frequent basis during the course of therapy, we can precisely adjust therapeutic
regimens for individual patients. However, accurately measuring microRNA in blood requires an extremely high
limit of detection due to low concentrations, detection over a broad range of concentrations, and high sequence-
specificity, attributes that are not currently possible for routine screening of fingerstick blood samples using
standard methods of detection, such as PCR. Toward this end, our clinical needs have inspired a new form of
assay to measure nucleic acids in blood through direct molecular counting in a microscope. This is now possible
because we have developed novel ways to amplify the signals from individual molecules through a series of
synergistic technologies, including light-emitting quantum dots, electric field-enhancing photonic crystals, and
single-step sequence-specific enzymatic growth of microRNA. We now will combine these technologies to set
the stage for measurement of microRNA using low-cost equipment that is already available in clinical diagnostic
laboratories to minimize translational barriers to clinical adoption. To achieve these goals, our multi-investigator
team has extensive expertise in probes for single-molecule imaging (Andrew Smith), optical detection in low-
cost devices (Brian Cunningham), clinical oncology (Manish Kohli), biomarker discovery (Liang Wang), and
epidemiology/biostatistics (Rebecca Smith). We will optimize our platform using a combination of synthetic and
clinical blood specimens and thoroughly analyze the sequence selectivity of our assay, particularly focusing on
microRNA variants, and closely compare our results with those from quantitative PCR assays. By the end of this
award period, we expect to have developed the first direct-readout microRNA assay for use in human samples
that is compatible with low-cost equipment, optimized the synergistic integration between quantum dots and
photonic crystals, and measured, for the first time, the precise (digital) concentrations of microRNA in the blood
of 100 subjects, prospectively enrolled and followed over 6 days each during the course of standard of care
treatments for which no predictive or prognostic biomarkers currently exist in the treatment of metastatic prostate
cancer. If successful, the outcome of this work will fill a major clinical gap in knowledge of how to match and
finely tune treatments to individual molecular profiles.
摘要
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(1)
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Andrew Michael Smith其他文献
Andrew Michael Smith的其他文献
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{{ truncateString('Andrew Michael Smith', 18)}}的其他基金
Hyperplexed Quantum Dots for Multidimensional Cell Classification in Intact Tissue
用于完整组织中多维细胞分类的超复合量子点
- 批准号:
10317961 - 财政年份:2021
- 资助金额:
$ 37.64万 - 项目类别:
Hyperplexed Quantum Dots for Multidimensional Cell Classification in Intact Tissue
用于完整组织中多维细胞分类的超复合量子点
- 批准号:
10450143 - 财政年份:2021
- 资助金额:
$ 37.64万 - 项目类别:
Hyperplexed Quantum Dots for Multidimensional Cell Classification in Intact Tissue
用于完整组织中多维细胞分类的超复合量子点
- 批准号:
10597685 - 财政年份:2021
- 资助金额:
$ 37.64万 - 项目类别:
Advanced Molecular Probes and Cell Engineering Tools for Accurate Single-Molecule Analysis of Signaling in Individual Cells
用于对单个细胞信号传导进行精确单分子分析的先进分子探针和细胞工程工具
- 批准号:
10363683 - 财政年份:2019
- 资助金额:
$ 37.64万 - 项目类别:
Targeted Drug Delivery to Adipose Tissue Macrophages in Obesity
肥胖症中脂肪组织巨噬细胞的靶向药物递送
- 批准号:
9354476 - 财政年份:2016
- 资助金额:
$ 37.64万 - 项目类别:
Targeted Drug Delivery to Adipose Tissue Macrophages in Obesity
肥胖症中脂肪组织巨噬细胞的靶向药物递送
- 批准号:
9763348 - 财政年份:2016
- 资助金额:
$ 37.64万 - 项目类别:
Next-Generation Quantum Dots for Molecular and Cellular Imaging of Cancer
用于癌症分子和细胞成像的下一代量子点
- 批准号:
8137827 - 财政年份:2010
- 资助金额:
$ 37.64万 - 项目类别:
Next-Generation Quantum Dots for Molecular and Cellular Imaging of Cancer
用于癌症分子和细胞成像的下一代量子点
- 批准号:
8009750 - 财政年份:2010
- 资助金额:
$ 37.64万 - 项目类别:
Next-Generation Quantum Dots for Molecular and Cellular Imaging of Cancer
用于癌症分子和细胞成像的下一代量子点
- 批准号:
8547022 - 财政年份:2010
- 资助金额:
$ 37.64万 - 项目类别:
Next-Generation Quantum Dots for Molecular and Cellular Imaging of Cancer
用于癌症分子和细胞成像的下一代量子点
- 批准号:
8466012 - 财政年份:2010
- 资助金额:
$ 37.64万 - 项目类别:
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