Novel Approaches to detect and treat sepsis

检测和治疗脓毒症的新方法

• 批准号: 10663361
• 负责人: Juhong Chen
• 金额: --
• 依托单位: VIRGINIA POLYTECHNIC INST AND ST UNIV
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10663361
• 关键词: Address; Bacteria; Bacterial Infections; Bacteriophage M13; Bacteriophages; Binding; Biomedical Research; Blood specimen; CRISPR/Cas technology; Capsid Proteins; Cause of Death; Cessation of life; Clinical; Clustered Regularly Interspaced Short Palindromic Repeats; Cobalt; Communities; Devices; Diagnosis; Disease; Engineering; Environmental Monitoring; Fiber; Food Safety; Goals; Hospital Mortality; Hospitalization; Hybrids; Life; Magnetic nanoparticles; Pathogen detection; Patients; Proteins; Public Health; Research; Resource-limited setting; Sampling; Sensitivity and Specificity; Sepsis; System; Tail; Technology; Testing; United States; Vision; Work; combat; improved; microfluidic technology; nanobodies; novel; novel strategies; pathogen; pathogenic bacteria; portability; programs; tool

Project Summary/Abstract: Background. Sepsis, a severe and life-threatening condition, is one of the most common causes of death in hospitalized patients. Sepsis is generally caused by bacterial infection, including both Gram-negative and positive bacteria. In the United States, the hospital mortality rate of patients with sepsis could be as high as 41.1%, which accounts for more than 250,000 deaths and $20 billion loss annually. Due to the inadequate sensitivity and specificity of the current technologies, there is no global standard for sepsis diagnosis. In this project, the PI has the ambition to address the critical bottlenecks specifically of concern in sepsis testing using: 1) hybrid bio-inorganic nanobots, 2) CRISPR-based devices, and 3) CRISPR-equipped engineered phages. Goals for the next five years. Our first goal is to engineer phage M13 with nanobodies on the capsid protein pVIII and his-tags on the tail fiber protein pIII. After binding cobalt-coated magnetic nanoparticles, the resulting hybrid bio-inorganic nanobots will be used to concentrate and purify pathogens from blood samples. Capture efficiency will be investigated using spiked samples and then proceed to clinical ones. Taking advantage of CRISPR and microfluidic technologies, the second goal is to fabricate portable devices to detect sepsis-related pathogens, which can be used in resource-limited settings. The last goal is to engineer phages with different CRISPR systems, that can be used to detect and combat sepsis-related bacterial pathogens. Towards the end of the fifth year, we will have integrated these technologies as a robust tool for sepsis diagnosis. Overall vision of the research program. The technologies we are developing will have a broad impact on the biomedical research communities to detect and treat sepsis, even for other diseases. Our developed technologies can also advance pathogen detection in other fields, such as food safety and environmental monitoring.

项目摘要/摘要： 背景。败血症是一种严重而威胁生命的状况，是最常见的死亡原因之一 住院的患者。脓毒症通常是由细菌感染引起的，包括革兰氏阴性症和 阳性细菌。在美国，败血症患者的医院死亡率可能高 41.1％，每年占死亡人数超过25万美元，损失200亿美元。由于不足 当前技术的敏感性和特异性，没有脓毒症诊断的全球标准。在这个 项目，PI具有针对败血症测试中关注的关键瓶颈的野心：使用： 1）混合生物无机纳米机器人，2）基于CRISPR的设备和3）配备CRISPR的工程噬菌体。 未来五年的目标。我们的第一个目标是用粘膜蛋白上的纳米生物形成来设计噬菌体M13 PVIII和HIS标签在尾纤维蛋白PIII上。结合钴粘的磁性纳米颗粒后，产生的 杂交生物无机纳米机器人将用于从血液样本中浓缩和纯化病原体。捕获 效率将使用峰值样品研究，然后继续进行临床。利用 CRISPR和微流体技术，第二个目标是制造便携式设备以检测败血症有关 病原体，可用于资源有限的设置。最后一个目标是设计不同的噬菌体 CRISPR系统，可用于检测和对抗败血症相关的细菌病原体。末尾 在第五年中，我们将将这些技术作为脓毒症诊断的强大工具集成。 研究计划的整体愿景。我们正在开发的技术将对 生物医学研究社区，即使是其他疾病，也可以检测和治疗败血症。我们发达的 技术还可以在其他领域（例如食品安全和环境）中提高病原体检测 监视。