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:10362538
- 负责人:
- 金额:$ 30.83万
- 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 2024-02-29
- 项目状态:已结题
- 来源:
- 关键词:AcetatesAdoptionAffectAftercareAwardBiological AssayBiological MarkersBiometryBloodBlood specimenCancer PatientClinicalClinical DataClinical OncologyClinical TrialsClosure by clampCollectionCouplingCrystallizationDetectionDevicesDiagnosisDiseaseDropsEffectivenessElectronicsEngineeringEnrollmentEpidemiologistEpidemiologyEquilibriumEquipmentGeneticGoalsGrowthHomeHumanIndividualInstitutional Review BoardsInterventionKnowledgeLabelLaboratoriesLengthLightMalignant NeoplasmsMeasurementMeasuresMetastatic Prostate CancerMicroRNAsMicroscopeMolecularMolecular 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 diagnosticscostdensitydesigndetection limitdetection methoddigitaldocetaxeldrug efficacyelectric fieldindividual patientinsightinstrumentinterestmolecular imagingnanoprobenew technologynovelphotonicsportabilitypredicting responsepredictive markerprospectiverapid techniqueratiometricresponseroutine screeningsingle moleculestandard of caresuccesstranslational barriertumortumor 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.
抽象的
该提案的主要目标是开发一种新技术,该技术可以允许患者反复测量
每天从一滴血液中产生的基于核酸的癌症生物标志物。该测定正在开发
用于确定药物治疗效率的特定临床应用,预后进行生存和监测 -
通过评估从肿瘤中脱落到癌症患者血液中的候选核酸来治疗干预。
由于我们的团队最近与生存有着非常密切的关系,我们专注于检测microRNA
针对转移性前列腺癌患者鉴定。我们通过测量的浓度来假设
在治疗过程中,这些标记在患者中经常进行,我们可以精确调整治疗性
单个患者的方案。但是,准确测量血液中的microRNA需要极高的
由于低浓度,浓度范围较高的检测而引起的检测极限,高序列 -
特异性,目前不可能使用针对指定血样的属性
标准检测方法,例如PCR。为此,我们的临床需求激发了一种新形式
测定通过显微镜中直接分子计数测量血液中核酸的测定。现在有可能
因为我们已经开发了新颖的方法来通过一系列来扩增单个分子的信号
协同技术,包括发光量子点,增强电场的光子晶体和
microRNA的单步序列特异性酶生长。我们现在将结合这些技术来设置
使用临床诊断中已经可用的低成本设备测量microRNA的阶段
实验室,以最大程度地减少临床采用的转化障碍。为了实现这些目标,我们
团队在单分子成像(安德鲁·史密斯)的探针方面拥有广泛的专业知识,低 -
成本设备(Brian Cunningham),临床肿瘤学(Manish Kohli),生物标志物发现(Liang Wang)和
流行病学/生物统计学(丽贝卡·史密斯)。我们将使用合成和合成的组合优化我们的平台
临床血液标本并彻底分析我们测定的序列选择性,尤其是专注于
microRNA变体,并将我们的结果与定量PCR分析的结果进行了比较。到最后
奖励期,我们希望已经开发了第一个直接阅读的microRNA分析,用于人类样品
这与低成本设备兼容,优化了量子点和
光子晶体,并首次测量了血液中microRNA的精确(数字)浓度
在护理标准过程中,有100名受试者被前景入学并遵循6天
当前在转移性前列腺治疗中,目前没有预测性或预后生物标志物的治疗方法
癌症。如果成功,这项工作的结果将填补有关如何匹配和
对单个分子特征进行细微的处理。
项目成果
期刊论文数量(9)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Label-Free Digital Detection of Intact Virions by Enhanced Scattering Microscopy.
- DOI:10.1021/jacs.1c09579
- 发表时间:2022-02-02
- 期刊:
- 影响因子:15
- 作者:Li, Nantao;Wang, Xiaojing;Tibbs, Joseph;Che, Congnyu;Peinetti, Ana Sol;Zhao, Bin;Liu, Leyang;Barya, Priyash;Cooper, Laura;Rong, Lijun;Wang, Xing;Lu, Yi;Cunningham, Brian T.
- 通讯作者:Cunningham, Brian T.
Expanding the Dynamic Range of Fluorescence Assays through Single-Molecule Counting and Intensity Calibration.
- DOI:10.1021/jacs.8b08879
- 发表时间:2018-10-24
- 期刊:
- 影响因子:15
- 作者:Smith L;Kohli M;Smith AM
- 通讯作者:Smith AM
Digital and Absolute Assays for Low Abundance Molecular Biomarkers.
低丰度分子生物标志物的数字和绝对测定。
- DOI:10.1021/acs.accounts.3c00030
- 发表时间:2023
- 期刊:
- 影响因子:18.3
- 作者:Kuo,Chia-Wei;Smith,AndrewM
- 通讯作者:Smith,AndrewM
Photonic crystal enhanced fluorescence emission and blinking suppression for single quantum dot digital resolution biosensing.
- DOI:10.1038/s41467-022-32387-w
- 发表时间:2022-08-08
- 期刊:
- 影响因子:16.6
- 作者:Xiong, Yanyu;Huang, Qinglan;Canady, Taylor D.;Barya, Priyash;Liu, Shengyan;Arogundade, Opeyemi H.;Race, Caitlin M.;Che, Congnyu;Wang, Xiaojing;Zhou, Lifeng;Wang, Xing;Kohli, Manish;Smith, Andrew M.;Cunningham, Brian T.
- 通讯作者:Cunningham, Brian T.
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Manish Kohli其他文献
Manish Kohli的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Manish Kohli', 18)}}的其他基金
Digital Multiplexed Analysis of Circulating Nucleic Acids in Small-Volume Blood Specimens
小体积血液样本中循环核酸的数字多重分析
- 批准号:
10467839 - 财政年份:2022
- 资助金额:
$ 30.83万 - 项目类别:
Digital Multiplexed Analysis of Circulating Nucleic Acids in Small-Volume Blood Specimens
小体积血液样本中循环核酸的数字多重分析
- 批准号:
10676313 - 财政年份:2022
- 资助金额:
$ 30.83万 - 项目类别:
Cell free nucleic acid-based biomarkers in advanced prostate cancer
晚期前列腺癌中基于无细胞核酸的生物标志物
- 批准号:
10240337 - 财政年份:2017
- 资助金额:
$ 30.83万 - 项目类别:
Cell free nucleic acid-based biomarkers in advanced prostate cancer
晚期前列腺癌中基于无细胞核酸的生物标志物
- 批准号:
9509379 - 财政年份:2017
- 资助金额:
$ 30.83万 - 项目类别:
Cell free nucleic acid-based biomarkers in advanced prostate cancer
晚期前列腺癌中基于无细胞核酸的生物标志物
- 批准号:
10220351 - 财政年份:2017
- 资助金额:
$ 30.83万 - 项目类别:
Cell free nucleic acid-based biomarkers in advanced prostate cancer
晚期前列腺癌中基于无细胞核酸的生物标志物
- 批准号:
10471263 - 财政年份:2017
- 资助金额:
$ 30.83万 - 项目类别:
Cell free nucleic acid-based biomarkers in advanced prostate cancer
晚期前列腺癌中基于无细胞核酸的生物标志物
- 批准号:
9751257 - 财政年份:2017
- 资助金额:
$ 30.83万 - 项目类别:
A Proteomics Approach for Identifying Predictive Factors to Androgen Deprivation
确定雄激素剥夺预测因素的蛋白质组学方法
- 批准号:
7894667 - 财政年份:2009
- 资助金额:
$ 30.83万 - 项目类别:
A Proteomics Approach for Identifying Predictive Factors to Androgen Deprivation
确定雄激素剥夺预测因素的蛋白质组学方法
- 批准号:
7738853 - 财政年份:2009
- 资助金额:
$ 30.83万 - 项目类别:
相似国自然基金
采用积分投影模型解析克隆生长对加拿大一枝黄花种群动态的影响
- 批准号:32301322
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
山丘区农户生计分化对水保措施采用的影响及其调控对策
- 批准号:42377321
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
跨期决策中偏好反转的影响因素及作用机制:采用体验式实验范式的综合研究
- 批准号:72271190
- 批准年份:2022
- 资助金额:43 万元
- 项目类别:面上项目
农民合作社视角下组织支持、个人规范对农户化肥农药减量增效技术采用行为的影响机制研究
- 批准号:72103054
- 批准年份:2021
- 资助金额:30 万元
- 项目类别:青年科学基金项目
采用磁共振技术研究帕金森病蓝斑和黑质神经退变及其对大脑结构功能的影响
- 批准号:
- 批准年份:2021
- 资助金额:55 万元
- 项目类别:面上项目
相似海外基金
Mental Health and Occupational Functioning in Nurses: An investigation of anxiety sensitivity and factors affecting future use of an mHealth intervention
护士的心理健康和职业功能:焦虑敏感性和影响未来使用移动健康干预措施的因素的调查
- 批准号:
10826673 - 财政年份:2024
- 资助金额:
$ 30.83万 - 项目类别:
Implementation of Innovative Treatment for Moral Injury Syndrome: A Hybrid Type 2 Study
道德伤害综合症创新治疗的实施:2 型混合研究
- 批准号:
10752930 - 财政年份:2024
- 资助金额:
$ 30.83万 - 项目类别:
Leveraging COVID-19 to modernize depression care for VA primary care populations
利用 COVID-19 实现 VA 初级保健人群的抑郁症护理现代化
- 批准号:
10636681 - 财政年份:2023
- 资助金额:
$ 30.83万 - 项目类别:
Efficacy and implementation of exercise-based smoking cessation treatment for adults with high anxiety sensitivity
以运动为基础的戒烟治疗对高焦虑敏感性成人的疗效和实施
- 批准号:
10660767 - 财政年份:2023
- 资助金额:
$ 30.83万 - 项目类别:
Team Support to Improve Glycemic Control Using CGM in Diverse Populations (TEAM CGM)
团队支持在不同人群中使用 CGM 改善血糖控制 (TEAM CGM)
- 批准号:
10659721 - 财政年份:2023
- 资助金额:
$ 30.83万 - 项目类别: