Isothermal Chain Reaction (ICR) Rapid and Early Detection of Pathogens for Sepsis Pont-of-Care Testing, Stratification, and Monitoring

等温链反应 (ICR) 快速、早期检测病原体，用于脓毒症即时护理测试、分层和监测

• 批准号: 9200259
• 负责人: Ricardo Mancebo
• 金额: $ 30万
• 依托单位: GENENDEAVOR, LLC
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9200259
• 关键词: Address; Bacteremia; Bedside Testings; Benchmarking; Biological Assay; Biological Markers; Biomedical Research; Biotechnology; Blood; Blood specimen; Budgets; Caring; Chemistry; Clinic; Clinical; Communicable Diseases; Complementary DNA; DNA; Detection; Development; Diagnostic; Disease; Early Diagnosis; Early identification; Ensure; Enzyme Inhibitor Drugs; Enzyme Inhibitors; Enzymes; Fluorescence; Foundations; Genetic screening method; Healthcare; Hereditary Disease; Hospitals; Infectious Agent; Intervention; Laboratories; Lead; Legal patent; Medical; Medical Records; Methods; Monitor; Mutation; Nucleic Acid Amplification Tests; Nucleic Acids; Nucleotides; Oligonucleotides; Outcome; Pathogen detection; Patients; Performance; Phase; Physicians' Offices; Population; Preparation; Procedures; Reaction; Reagent; Reporting; Resistance; Resolution; Sampling; Screening for cancer; Sensitivity and Specificity; Sepsis; Sepsis Syndrome; Septic Shock; Severities; Specificity; Specimen; Speed; Staging; Statistical Data Interpretation; Stratification; System; Technology; Testing; Therapeutic Intervention; Time; Treatment outcome; Triage; Whole Blood; Work; base; cost; cost effective; design; experience; improved; innovation; instrument; mutant; next generation; next generation sequencing; novel; pathogen; point of care; rapid detection; research clinical testing; research study; screening; standard of care; technology development

Project Summary Objectives: The long-term objective of this application is to develop novel products for routine point-of-care (POC) genetic testing, ranging from pathogen identification to early cancer detection by using an innovative biotechnology called, Isothermal Chain Reaction (ICR). ICR is a disruptive and enabling technology platform that will offer a new class of reagents relevant to biomedical research and medical healthcare. ICR does not require any enzymes, primers, nucleotides, master mixes, extension reactions, cDNA intermediates, or thermocycling. These benefits overcome constraints of PCR-based technologies by being resistant to enzyme inhibitors found in laboratory samples and clinical specimens, having higher specificity for rare mutations, and lowering reagent costs. ICR is anticipated to enable selective, rapid, and affordable biomarker detection without having to invest in costly instruments and labor-intensive sample preparation procedures. The envisioned products will be assays, panels, and kits for the early detection of infectious and genetic diseases in non-laboratory settings. Specific Aims: 1. Development of ICR probes to sepsis target sequences: We will design and develop ICR assays to rapidly and isothermally detect synthetic target sequences associated with sepsis in a mixed population of templates in less than 10 minutes under isothermal conditions, without enzymes, primers, nucleotides, or master mixes. 2. Identification of known sepsis pathogens in blood samples: We will use ICR assays from Specific Aim 1 to identify known sepsis pathogens from retrospective blood samples. ICR results will be benchmarked to blood cultures to demonstrate the feasibility of using ICR for rapid early detection of sepsis biomarkers. 3. Identification of unknown sepsis pathogens in blood samples: We will use ICR assays from Specific Aim 1 to identify unknown sepsis pathogens from retrospective blood samples. ICR results will be benchmarked to blood cultures to demonstrate the feasibility that ICR has enhanced selectivity to detect pathogens missed by blood culture methods, and ICR is more amenable to point-of-care sepsis testing. Impact: Accomplishing the Specific Aims could significantly impact rapid and early detection of sepsis pathogens when therapeutic interventions are much more effective, and enable routine clinical testing and screening of the disease to improve clinical triage decisions, routine monitoring, and treatment outcomes.

项目摘要 目的： 本申请的长期目标是开发用于常规床旁（POC）遗传学检查的新产品。 检测，从病原体鉴定到使用创新生物技术进行早期癌症检测， 等温链反应（Isothermal Chain Reaction，ICR）ICR是一个颠覆性的支持技术平台， 与生物医学研究和医疗保健相关的新型试剂。ICR不需要任何 酶、引物、核苷酸、主混合物、延伸反应、cDNA中间体或热循环。 这些益处克服了基于PCR技术的限制，因为它们对发现的酶抑制剂具有抗性。 在实验室样本和临床标本中，对罕见突变具有更高的特异性， 成本ICR有望实现选择性，快速和负担得起的生物标志物检测，而无需投资 昂贵的仪器和劳动密集型的样品制备程序。设想的产品将是 用于在非实验室环境中早期检测传染病和遗传病的检测试剂盒、检测板和试剂盒。 具体目标： 1.针对脓毒症靶序列的ICR探针的开发：我们将设计和开发ICR检测， 并等温检测与败血症相关的合成靶序列， 在等温条件下，在不到10分钟的时间内，在没有酶、引物、核苷酸或 大师混音 2.血液样本中已知脓毒症病原体的鉴定：我们将使用特定目标1至 从回顾性血液样本中鉴定已知脓毒症病原体。将对ICR结果进行基准测试， 血培养证明使用ICR快速早期检测脓毒症生物标志物的可行性。 3.血液样本中未知脓毒症病原体的鉴定：我们将使用来自Specific Aim 1的ICR检测试剂盒 从回顾性血液样本中鉴定未知的脓毒症病原体。ICR结果将是 以血培养为基准，以证明ICR增强了检测选择性的可行性 血液培养方法遗漏的病原体，ICR更适合于护理点败血症检测。 影响： 实现特定目标可以显著影响脓毒症病原体的快速和早期检测 当治疗干预更加有效，并使常规临床测试和筛查成为可能时， 以改善临床分诊决策、常规监测和治疗结果。