Quantitation and Genotyping of HCV RNA by Time Resolved Lanthanide Luminescence

通过时间分辨镧系元素发光对 HCV RNA 进行定量和基因分型

• 批准号: 8466924
• 负责人: ANDREW M ARSHAM
• 金额: $ 30万
• 依托单位: WAVE 80 BIOSCIENCES, INC.
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-07 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8466924
• 关键词: Accounting; Affect; Algorithms; Antiviral Therapy; Bedside Testings; Biological Assay; Blood; Blood capillaries; Cancer Etiology; Caring; Cessation of life; Characteristics; Chemistry; Chronic Hepatitis; Chronic Hepatitis C; Cirrhosis; Clinical; Detection; Development; Devices; Diagnostic tests; Dyes; Engineering; Environment; Europium; FDA approved; Fingerprint; Freeze Drying; Genotype; HIV; Healthcare; Healthcare Systems; Hepatitis C virus; Hospitalization; Hospitals; Individual; Infection; Insurance Coverage; Interferons; Laboratories; Lanthanoid Series Elements; Lead; Left; Liver diseases; Malignant neoplasm of liver; Measurement; Methods; Molecular; Mono-S; Noise; Oligonucleotide Probes; Outcome; Patient Care; Patient Monitoring; Patients; Performance; Phase; Preparation; Primary carcinoma of the liver cells; Process; RNA; RNA Viruses; Reagent; Regimen; Ribavirin; Risk; Rosa; Running; Sampling; Signal Transduction; Singlet Oxygen; Speed; Staging; Structure; System; Tail; Technology; Terbium; Testing; Therapeutic; Time; Treatment outcome; Underinsured; Uninsured; United States; United States Department of Veterans Affairs; Viral Load result; Viral load measurement; Virus; Whole Blood; Work; base; capillary; chelation; clinically relevant; computerized data processing; cost; cost effective; design; ethnic minority population; improved; innovation; light emission; luminescence; point of care; programs; prototype; response; screening; standard of care; success; tool; urban Native American; verification and validation; viral RNA

DESCRIPTION (provided by applicant): Hepatitis C virus (HCV) is a single-stranded RNA virus of roughly 9.4 kb estimated to affect 200 million people worldwide. In the U.S., where it is estimated that 4.1 million are infected, HCV accounts for 60-70% of chronic hepatitis and 50% of cirrhosis, end-stage liver disease, and hepatocellular carcinoma, causing an estimated 12,000 deaths annually. From 1994 to 2007, annual hospitalizations for HCV rose 10.3-fold, while total healthcare spending increased from $627 million to $6.9 billion in HCV mono-infected patients and from $63 million to $655 million in HIV/HCV co-infected patients. Approximately 75% of HCV-infected people in the U.S. are unaware of their condition and are at increased risk for late-stage complications of cirrhosis and liver cancer. Patient access outside of institutional healthcare systems is limited by the high cost of testing and treatment, particularly for the uninsured and underinsured - only 54% of HCV treatment candidates have any type of insurance coverage. Patients at Veterans Administration hospitals, urban Native American populations, and ethnic minorities in the U.S. have disproportionately high rates of chronic HCV infection and complications. Current standard-of-care combination antiviral therapy (ribavirin/peg-interferon) eradicates HCV in many patients, while newly FDA-approved HCV-specific therapies greatly increase the likelihood and speed of positive treatment outcomes. Prerequisites for successful administration of current and emerging therapeutic regimens are genotyping and measurement of viral loads, both of which help determine treatment course and duration. Determination of baseline HCV RNA levels is critical for monitoring patient response to therapy, and recent evidence suggests that personalizing treatment based on initial viral load and virological response increases success rates. As the HCV standard of care evolves, identifying people infected with HCV takes on even greater importance, including a renewed push for screening programs to identify and treat undiagnosed patients, as well as for rapid point of care testing. This proposal develops the EOSCAPE-CLEF (Chelated Lanthanide Emission Fingerprinting), a low-cost, point of care (POC) alternative to conventional HCV RNA testing, combining quantitative detection by signal amplification with sensitive and specific genotyping using a pioneering signal processing algorithm based on the characteristic light emission profiles of individual chelate-lanthanide pairs conjugated to a stringent molecular beacon-style probe. The enclosed-cartridge format system is anticipated to reduce costs from a combined $400 for quantitation and genotyping to less than $35 while also reducing the turnaround time to 30 minutes. The assay runs in a single-use enclosed cartridge based on the Applicant Organization's monolithic slit capillary array fluidic microactuator (mSCAFA) technology.

描述（由申请人提供）：丙型肝炎病毒（HCV）是一种单链的RNA病毒，大约9.4 kb估计会影响全球2亿人。在美国，据估计感染了410万次，HCV占慢性肝炎的60-70％，肝硬化，末期肝病和肝细胞癌的50％占每年12,000例死亡。从1994年到2007年，HCV的年度住院时间增长了103倍，而总医疗保健支出从6.27亿美元增加到69亿美元的HCV单人感染患者，从6,300万美元增加到6.55亿美元增加到6.55亿美元的HIV/HCV共同感染的患者。在美国，大约75％的HCV感染者没有意识到自己的状况，并且患有肝硬化后期并发症的风险增加。患者进入机构之外 医疗保健系统受测试和治疗成本高的限制，尤其是对于未投保和保险不足的人 - 只有54％的HCV治疗候选者具有任何类型的保险范围。美国退伍军人管理医院，美国原住民人口和美国少数民族的患者的慢性HCV感染和并发症的比例高。 当前的护理标准组合抗病毒疗法（利巴韦林/PEG间隙）消除了许多患者的HCV，而新近FDA批准的HCV特异性疗法大大提高了阳性治疗结果的可能性和速度。成功施用当前和新兴治疗方案的先决条件是病毒负荷的基因分型和测量，这两者都有助于确定治疗过程和持续时间。基线HCV RNA水平的确定对于监测患者对治疗的反应至关重要，最近的证据表明，基于初始病毒载荷和病毒学反应的个性化治疗可以提高成功率。随着HCV护理标准的发展，识别感染HCV的人的重要性更大，包括重新推动筛查计划以识别和治疗未诊断未诊断的患者以及快速的护理测试。 This proposal develops the EOSCAPE-CLEF (Chelated Lanthanide Emission Fingerprinting), a low-cost, point of care (POC) alternative to conventional HCV RNA testing, combining quantitative detection by signal amplification with sensitive and specific genotyping using a pioneering signal processing algorithm based on the characteristic light emission profiles of individual chelate-lanthanide pairs conjugated to a严格的分子信标探针。预计，封闭式式式式式式格式系统将使成本从合计的400美元降低到定量和基因分型少于35美元，同时还将周转时间降低到30分钟。该测定法基于申请人组织的单片缝隙毛细管阵列流体微启动器（MSCAFA）技术，以一次性封闭的墨盒进行运行。