Novel Approaches to detect and treat sepsis

检测和治疗脓毒症的新方法

• 批准号: 10500895
• 负责人: Juhong Chen
• 金额: $ 38.99万
• 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 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10500895
• 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; 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; base; 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。败血症是一种严重且危及生命的疾病，是最常见的死亡原因之一 住院病人。脓毒症一般是由细菌感染引起，包括革兰氏阴性菌和革兰氏阴性菌。 阳性细菌。在美国，败血症患者的医院死亡率可能高达 41.1%，每年造成超过 25 万人死亡和 200 亿美元损失。由于不足 就目前技术的敏感性和特异性而言，脓毒症诊断尚无全球标准。在这个 项目中，PI 致力于解决脓毒症检测中特​​别关注的关键瓶颈，使用： 1) 混合生物-无机纳米机器人，2) 基于 CRISPR 的设备，以及 3) 配备 CRISPR 的工程噬菌体。 未来五年的目标。我们的首要目标是在衣壳蛋白上设计带有纳米抗体的噬菌体 M13 尾部纤维蛋白 pIII 上的 pVIII 和 his 标签。结合钴包覆的磁性纳米粒子后，所得的 混合生物-无机纳米机器人将用于浓缩和纯化血液样本中的病原体。捕获 将使用加标样品研究效率，然后进行临床研究。利用 CRISPR和微流控技术，第二个目标是制造便携式设备来检测脓毒症相关疾病 病原体，可用于资源有限的环境。最后一个目标是设计具有不同特性的噬菌体 CRISPR 系统，可用于检测和对抗脓毒症相关细菌病原体。接近尾声 第五年，我们将整合这些技术，作为脓毒症诊断的强大工具。 研究计划的总体愿景。我们正在开发的技术将对 生物医学研究界检测和治疗败血症，甚至其他疾病。我们开发的 技术还可以推进其他领域的病原体检测，例如食品安全和环境 监控。