Novel PhageLock assay to measure hepcidin for clinical monitoring

新型 PhageLock 测定法可测量铁调素以进行临床监测

基本信息

批准号：
9462254
负责人：
Martyn Darby
金额：
$ 33.3万
依托单位：
AFFINERGY, LLC
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-16 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9462254
关键词：
Address Affinity Anemia due to Chronic Disorder Antibodies Back Bacteriophages Binding Biological Assay Blood Circulation Characteristics Clinical Clinical Chemistry Clinical Management Complex Detection Development Diagnosis Disease Ensure Enzyme-Linked Immunosorbent Assay FDA approved Goals Guidelines Heart Heart Diseases Hereditary hemochromatosis Hormones Hypoxia Immunoassay Infection Inflammatory Institutes Iron Iron Metabolism Disorders Iron Overload Iron deficiency anemia Kidney Diseases Laboratories Malignant Neoplasms Measurement Measures Methods Monitor Notification One-Step dentin bonding system Patients Peptides Performance Phage Display Phase Plasma Production Protocols documentation Reagent Reporting Research Personnel Sampling Serum Signal Transduction Specificity Specimen Technology Testing base cationic antimicrobial protein CAP 37 clinically relevant cost effective hepcidin immunogenicity innovation iron deficiency iron metabolism novel overexpression peptide hormone reagent testing scale up success

项目摘要

SUMMARY/ABSTRACT Hepcidin is the peptide hormone responsible for regulating circulating iron concentrations. Overexpression of hepcidin results in severe iron deficiency and anemia, whereas hepcidin deficiency leads to iron overload. Not surprisingly, abnormalities in hepcidin production and circulating concentrations are highly correlated with various disease states such as renal disease, cancer, hereditary hemochromatosis, hypoxia, anemia of inflammation, infection, inflammatory diseases, and heart disease. Accurate methods for detecting hepcidin in serum will lead to improvements in our understanding, diagnosis, and clinical management of iron metabolism disorders. Unfortunately, there is no FDA-approved assay for measuring hepcidin levels in plasma. The development of a clinically relevant hepcidin assay has been hindered by hepcidin’s very low immunogenicity, making it extremely challenging to produce antibodies against the hormone. The few immunoassays that do exist are poorly characterized in terms of specificity, and they struggle to differentiate hepcidin from the multiple inactive forms of the hormone that are found in the circulation. Affinergy plans to develop a phage-based clinical chemistry assay that will enable frequent, simple, and affordable monitoring of plasma hepcidin-25 levels. Using our core technology of phage display biopanning, we have already identified a proprietary “capture” peptide that binds to hepcidin-25. In this Phase 1 application, we intend to identify a hepcidin-25 specific “detection” phage and incorporate the hepcidin-25-binding peptide and phage in a rapid, easy-to-use sandwich ELISA-based assay. At the conclusion of Phase 1, we expect to have a technology that can be scaled up in Phase 2 for use by clinicians and researchers to measure hepcidin concentrations in plasma.

摘要/摘要铁调素是一种肽激素，负责调节循环铁浓度的过度表达。铁调素会导致严重的铁缺乏和贫血，而铁调素缺乏则不会导致铁过载。令人惊讶的是，铁调素产生和循环浓度的异常与各种疾病状态，如肾病、癌症、遗传性血色素沉着症、缺氧、贫血等炎症、感染、炎症性疾病和心脏病中铁调素的准确检测方法。血清将改善我们对铁代谢的理解、诊断和临床管理不幸的是，目前还没有 FDA 批准的测定血浆铁调素水平的方法。临床相关的铁调素检测方法的开发因铁调素的免疫原性极低而受到阻碍，这使得产生针对该激素的抗体变得极具挑战性。存在的特征在特异性方面很差，并且他们很难将铁调素与多种 Affinergy 计划开发一种基于噬菌体的激素。临床化学测定将实现频繁、简单且经济实惠的血浆监测使用我们的噬菌体展示生物淘选核心技术，我们已经确定了 hepcidin-25 水平。与 hepcidin-25 结合的专有“捕获”肽在这一阶段的应用中，我们打算鉴定一种 hepcidin-25 特异性“检测”噬菌体，并将 hepcidin-25 结合肽和噬菌体以快速、易于使用的基于 ELISA 的夹心检测在第一阶段结束时，我们期望拥有一种技术可以在第二阶段扩大规模，供信徒和研究人员使用，以测量铁调素浓度等离子体。