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

基本信息

批准号：
8315764
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
项目类别：
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/8315764
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 Screening procedure 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 standard of care success tool urban Native American verification and validation viral RNA

项目摘要

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. PUBLIC HEALTH RELEVANCE: Infection with the Hepatitis C virus (HCV) accounts for up to 50 percent of cirrhosis, end-stage liver disease, and liver cancer and causes an estimated 10,000 to 12,000 deaths annually in the United States and many times more than that globally. Successful treatment of HCV depends upon subtype identification and frequent measurement of the amount of virus in the blood through a specialized type diagnostic testing. This proposal will develop an innovative device for fast and inexpensive combined quantitation and genotyping of HCV from whole blood which will improve patient outcomes and reduce costs for HCV patient care both domestically and globally.

描述（由申请人提供）：丙型肝炎病毒（HCV）是一种大约 9.4 kb 的单链 RNA 病毒，估计影响全世界 2 亿人。在美国，估计有 410 万人被感染，HCV 占慢性肝炎的 60-70%，肝硬化、终末期肝病和肝细胞癌的 50%，每年估计导致 12,000 人死亡。从 1994 年到 2007 年，每年因丙肝病毒住院的人数增加了 10.3 倍，而丙肝病毒单一感染患者的医疗保健总支出从 6.27 亿美元增加到 69 亿美元，艾滋病毒/丙肝病毒双重感染患者的医疗保健总支出从 6300 万美元增加到 6.55 亿美元。在美国，大约 75% 的 HCV 感染者不知道自己的病情，并且发生肝硬化和肝癌晚期并发症的风险增加。患者在机构之外的访问医疗保健系统受到检测和治疗成本高昂的限制，特别是对于没有保险和保险不足的人来说 - 只有 54% 的 HCV 治疗候选人拥有任何类型的保险。美国退伍军人管理局医院的患者、城市美洲原住民和少数族裔的慢性丙型肝炎感染和并发症发生率异常高。目前的标准治疗联合抗病毒疗法（利巴韦林/聚乙二醇干扰素）可以根除许多患者的丙肝病毒，而 FDA 新批准的丙肝病毒特异性疗法大大增加了获得积极治疗结果的可能性和速度。成功实施当前和新兴治疗方案的先决条件是基因分型和病毒载量测量，这两者都有助于确定治疗过程和持续时间。确定基线 HCV RNA 水平对于监测患者对治疗的反应至关重要，最近的证据表明，基于初始病毒载量和病毒学反应的个性化治疗可提高成功率。随着 HCV 护理标准的发展，识别 HCV 感染者变得更加重要，包括重新推动筛查计划以识别和治疗未确诊患者，以及快速护理点检测。该提案开发了 EOSCAPE-CLEF（螯合镧系元素发射指纹图谱），这是一种替代传统 HCV RNA 检测的低成本即时护理 (POC) 替代方案，将信号放大定量检测与使用基于开创性信号处理算法的灵敏和特异性基因分型相结合。与严格的分子信标型探针缀合的各个螯合物-镧系元素对的特征光发射曲线。封闭式卡盒格式系统预计可将定量和基因分型的总成本从 400 美元降低至 35 美元以下，同时还将周转时间缩短至 30 分钟。该测定在基于申请人组织的单片狭缝毛细管阵列流体微致动器（mSCAFA）技术的一次性封闭盒中运行。公共卫生相关性：丙型肝炎病毒 (HCV) 感染导致肝硬化、终末期肝病和肝癌的比例高达 50%，在美国每年估计导致 10,000 至 12,000 人死亡，这一数字还要多出许多倍全球。 HCV 的成功治疗取决于亚型识别以及通过专门的类型诊断测试频繁测量血液中的病毒量。该提案将开发一种创新设备，用于对全血中的 HCV 进行快速且廉价的组合定量和基因分型，这将改善患者的治疗结果并降低国内和全球 HCV 患者护理的成本。