Rapid point-of-care molecular test for HCV VL

HCV VL 快速护理点分子检测

• 批准号: 10330833
• 负责人: Jay Kenneth Fisher
• 金额: $ 28.87万
• 依托单位: REDBUD LABS, INC.
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10330833
• 关键词: 5' Untranslated Regions; Affect; Algorithms; Antibodies; Antiviral Agents; Biological Assay; Blood; Chemistry; Cirrhosis; Clinic Visits; Cold Chains; Comprehensive Health Care; Detection; Development; Devices; Diagnosis; Diagnostic; Diagnostic tests; Diffusion; Digit structure; Disease; Electricity; Environment; Exposure to; Fluorescence; Funding; Future; Genotype; Goals; Gold; HCV screening; HIV; HIV-1; Hepatitis B Virus; Hepatitis C; Hepatitis C Antibodies; Hepatitis C Prevalence; Hepatitis C Therapy; Hepatitis C virus; High Prevalence; Individual; Infection; Inflammatory; Kinetics; Laboratories; Letters; Liver Failure; Liver diseases; Methods; Microfluidic Microchips; Microfluidics; Molecular; Nucleic Acid Amplification Tests; Nucleic Acids; Oranges; Patients; Performance; Phase; Polymerase; Population; Populations at Risk; Preparation; Primary carcinoma of the liver cells; Production; Quantitative Reverse Transcriptase PCR; Reagent; Resources; Rest; Routine Diagnostic Tests; Running; Sampling; Sensitivity and Specificity; Specificity; Specimen; System; Technology; Testing; Tube; Viral Load result; Viremia; Vulnerable Populations; Work; amplification detection; antibody test; assay development; base; comorbidity; cost; design; detection limit; diagnostic assay; follow-up; isothermal amplification; magnetic beads; nucleic acid purification; phase 2 study; point of care; programs; recombinase; risk minimization; scale up; success; treatment strategy

ABSTRACT Hepatitis C, the inflammatory liver disease caused by hepatitis C virus (HCV), claims approximately 400,000 lives each year from secondary hepatocellular carcinoma and cirrhosis-induced liver failure. Direct-acting antiviral agents can cure > 95% of the estimated 71 million cases of hepatitis C found globally, yet because of underdiagnosis, only 7% of patients are currently receiving treatment. The diagnostic testing algorithm for HCV necessitates multiple clinic visits. Individuals in vulnerable populations often lack the means to meet this high follow-up burden. Increasing the prevalence of HCV treatment to reflect the 95% cure rate requires simplification of diagnostic testing. To this end we will develop a sample-to-answer HCV viral load (VL) test that meets or exceeds the minimal acceptable criteria as defined by the hepatitis C global stakeholder consortium. To achieve this goal, we will combine Redbud Labs’ expertise in microfluidics and systems with the diagnostic assay development expertise of the Diagnostics Program at PATH (Seattle, WA). In Aim 1 Redbud Labs will optimize each assay step to the microfluidic environment using Redbud technologies and commercially available reagents. In Aim 2 PATH will design assay primers and probes. In Aim 3 Redbud Labs will validate the assay by performing it end-to-end using a breadboard system. Redbud technologies are production-ready, which will minimize the risk of degradation in assay performance as we move through cartridge integration in future Phase II work.

摘要 丙型肝炎是由丙型肝炎病毒（HCV）引起的炎症性肝病， 每年都有5000人死于继发性肝细胞癌和肝硬化引起的肝功能衰竭。直接作用 抗病毒药物可以治愈全球发现的7100万丙型肝炎病例中的95%以上，但由于 诊断不足，只有7%的患者目前正在接受治疗。HCV的诊断检测算法 需要多次门诊。弱势群体中的个人往往缺乏满足这一高需求的手段， 后续负担。提高HCV治疗的流行率以反映95%的治愈率需要简化 诊断测试。为此，我们将开发一种样本到答案的HCV病毒载量（VL）测试， 超过丙型肝炎全球利益相关者联盟定义的最低可接受标准。 为了实现这一目标，我们将联合收割机Redbud Labs在微流体和系统方面的专业知识与诊断技术相结合。 PATH（西雅图，华盛顿州）诊断项目的检测开发专业知识。在Aim 1中，Redbud Labs将 使用Redbud技术和商业上的微流体环境优化每个测定步骤 可用的试剂。在目标2中，PATH将设计检测试剂盒引物和探针。在Aim 3中，Redbud Labs将验证 通过使用试验板系统进行端到端的分析。Redbud的技术已经可以投入生产了 这将最大限度地减少当我们通过检测盒集成时检测性能下降的风险， 未来的第二阶段工作。