Paper-Based Nucleic Acid Amplification Test for Rapid Diagnosis of Hepatitis C Viral Infection
纸基核酸扩增测试快速诊断丙型肝炎病毒感染
基本信息
- 批准号:10430557
- 负责人:
- 金额:$ 18.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-02-01 至 2024-01-31
- 项目状态:已结题
- 来源:
- 关键词:Acute HepatitisAddressAdoptedAntiviral AgentsAwarenessBindingBiological AssayBlood specimenCaringCellular PhoneChargeChronic Hepatitis CCirrhosisClinicalClinical TrialsClustered Regularly Interspaced Short Palindromic RepeatsColorCommunicable DiseasesComplexContinuous CapillaryCouplingDNA PrimersDetectionDevice DesignsDevicesDiagnosisDiagnosticEarly DiagnosisEarly treatmentEnzymesFluorescenceFundingGenerationsGoalsGoldGuide RNAHepatitis BHepatitis CHepatitis C AntibodiesHepatitis C TherapyHepatitis C virusHumanImmuneInfectionMeasuresMedicalMembraneMethodsMonitorNucleic Acid Amplification TestsNucleic AcidsPaperPatientsPersonsPhasePoint of Care TechnologyPolymerasePolymerase Chain ReactionPopulationPricePrimary carcinoma of the liver cellsProcessPublic HealthRNARNA analysisRNA primersReactionReaction TimeReagentReportingResource-limited settingSamplingSchemeSensitivity and SpecificitySignal TransductionSiteSpecificityTechnologyTemperatureTestingTimeViral hepatitisViremiaVirus DiseasesVisitantibody testbasecostcost effectivedensitydesigndetection limitdetection sensitivitydiagnostic platformdiagnostic technologiesds-DNAimprovedinnovationlateral flow assayliver transplantationmHealthminiaturizenanoGoldnovelnovel diagnosticspoint of carepoint-of-care diagnosticspreventprototyperapid diagnosisrecombinaseside effectsuccesstechnology developmenttreatment siteviral RNA
项目摘要
Abstract
Chronic hepatitis C virus (HCV) infection is a leading cause of cirrhosis, hepatocellular carcinoma, and liver
transplantation. With the successful introduction in 2013 of a direct-acting antiviral (DAA) drug with few side
effects, an affordable price and a >90% cure rate for the treatment of HCV infection, WHO adopted the first-ever
global strategy for eliminating viral hepatitis as a public health problem by 2030. This ambitious goal will require
major efforts, not only to prevent new infections but also to diagnose those who are not yet aware of being
infected. It is estimated that of the 71 million people who are living with HCV infection, half are unaware of their
infection and are thus untreated. A key to providing medical care to this untreated population, and thus to
stopping spread of the infection, is to initiate immediate treatment on site once the infection is diagnosed during
a patient's regular visit to a doctor's office. This will require a rapid, cost-effective diagnostic platform that can be
used at the point of care (POC) and provide diagnostic results in <30 minutes. The current diagnostics, an initial
HCV antibody (Ab) test to document exposure followed by the more complex and expensive HCV RNA test to
confirm viremia, cannot meet the POC need. Since serum HCV RNA can be detected as early as 1-2 weeks
after infection, polymerase chain reaction (PCR) based RNA analysis is the gold standard method for HCV
diagnosis. However, implementation of PCR-based analysis at the POC is limited by its slow turnaround time
and high cost/efficacy ratio, especially in resource-poor settings. This proposal is aimed at filling the gap by
developing a novel diagnostic platform capable of identifying HCV infection in <20 minutes by integrating
recombinase polymerase amplification (RPA), CRISPR-Cas12a and a positively charged gold nanoparticle
(+GNP) based lateral flow assay (LFA) into a unified single-step assay for nucleic acid amplification (NAA) test.
To achieve the objective and address the technology challenges facing an LFA-based POC NAA test, this project
will implement several principal innovations: 1) use of RNA primers for RPA nucleic acid amplification to address
the incompatibility issue in unifying RPA and CRISPR-12a reactions, 2) selective transporting out of the charged
+GNPs released by the CRISPR amplification process to address the reagent/enzyme washout issue, 3) design
of novel target test lines with graded target-binding and an intrinsic reaction “timer” to address the quantification
issue associated with LFA-based nucleic acid diagnostic technology, and 4) miniaturized smartphone-based
detection, which will make HCV diagnosis more POC and mobile health compatible. We expect that successful
completion of this project will lead to a novel, robust, cost-effective POC technology for the rapid NAA diagnosis
of HCV infection, which will have broad positive impacts on the early diagnosis and treatment of HCV and other
infectious diseases.
摘要
慢性丙型肝炎病毒(HCV)感染是肝硬化、肝细胞癌和肝硬化的主要原因。
移植随着2013年成功推出一种副作用少的直接作用抗病毒(DAA)药物,
世界卫生组织首次采用了治疗丙型肝炎病毒感染的效果、实惠的价格和>90%的治愈率
到2030年消除病毒性肝炎这一公共卫生问题的全球战略。这一宏伟目标需要
这不仅是为了预防新的感染,也是为了诊断那些还没有意识到被感染的人。
感染了据估计,在7100万丙型肝炎病毒感染者中,有一半人不知道自己的病情。
感染,因此不能治疗。为这些未经治疗的人群提供医疗护理的关键,
停止感染的传播,是在感染被诊断出来后立即在现场进行治疗,
病人定期去看医生这将需要一个快速、具有成本效益的诊断平台,
在护理点(POC)使用,并在30分钟内提供诊断结果。目前的诊断,
HCV抗体(Ab)检测记录暴露,然后是更复杂和昂贵的HCV RNA检测,
确认病毒血症,不能满足POC需求。由于血清HCVRNA最早可在1-2周内检测到,
感染后,基于聚合酶链反应(PCR)的RNA分析是HCV的金标准方法
诊断.然而,在POC实施基于PCR的分析受到周转时间缓慢的限制
成本/效益比高,特别是在资源贫乏的环境中。这项建议旨在填补差距,
开发一种新的诊断平台,通过整合能够在20分钟内识别HCV感染,
重组酶聚合酶扩增(RPA)、CRISPR-Cas 12 a和带正电荷的金纳米颗粒
(+GNP)为基础的侧向流分析(LFA)为一个统一的单步分析核酸扩增(NAA)测试。
为了实现这一目标,并解决基于LFA的POC NAA测试所面临的技术挑战,
1)使用RNA引物进行RPA核酸扩增,以解决
在统一RPA和CRISPR-12 a反应中的不相容性问题,2)选择性运输出带电的
+由CRISPR扩增过程释放的GNP,以解决试剂/酶洗脱问题,3)设计
具有分级靶结合和固有反应“计时器”的新型靶测试线,以解决定量问题
与基于LFA核酸诊断技术相关的问题,以及4)基于微型智能手机的
检测,这将使HCV诊断更加POC和移动的健康兼容。我们期待成功
该项目的完成将为快速NAA诊断带来一种新颖、稳健、具有成本效益的POC技术
这将对HCV感染的早期诊断和治疗产生广泛的积极影响,
传染病
项目成果
期刊论文数量(0)
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{{ truncateString('WEN-JI DONG', 18)}}的其他基金
Paper-Based Nucleic Acid Amplification Test for Rapid Diagnosis of Hepatitis C Viral Infection
纸基核酸扩增测试快速诊断丙型肝炎病毒感染
- 批准号:
10558611 - 财政年份:2022
- 资助金额:
$ 18.41万 - 项目类别:
Two-Dimensional Multi-Stage Isotachophoretic Technology for Multiplex Analysis of Cancer Exosomes and Proteins Marker Panel
用于癌症外泌体和蛋白质标记物组多重分析的二维多级等速电泳技术
- 批准号:
10322022 - 财政年份:2021
- 资助金额:
$ 18.41万 - 项目类别:
Structural Kinetics of Thin Filament Regulation at Single Molecule Level
单分子水平细丝调控的结构动力学
- 批准号:
8445988 - 财政年份:2013
- 资助金额:
$ 18.41万 - 项目类别:
Structural Kinetics of Thin Filament Regulation at Single Molecule Level
单分子水平细丝调节的结构动力学
- 批准号:
8690957 - 财政年份:2013
- 资助金额:
$ 18.41万 - 项目类别:
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