权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Circulating Red Blood Cell Based Nanosensors for Continuous, Real-Time Drug Monitoring

基于循环红细胞的纳米传感器，用于连续、实时药物监测

基本信息

批准号：
10174441
负责人：
Heather A Clark
金额：
$ 21.11万
依托单位：
NORTHEASTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-02-01 至 2022-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10174441
关键词：
Adopted Animal Experimentation Animals Articular Range of Motion Base Pairing Biochemical Biological Biological Markers Blood Tests C-reactive protein COVID-19 Chemicals Coronavirus Infections DNA DNA Modification Process DNA Structure Detection Development Diagnostic Digestion Disease Drug Monitoring Early Diagnosis Environment Erythrocytes Event Ferritin Goals Immune system Immunologics Interferon Type II Interleukin-10 Interleukin-6 Laboratories Measurement Mechanics Methods Modification Monitor Morbidity - disease rate Nanostructures Nanotechnology Optics Organ Outcome Pathogenesis Pathogenicity Patients Performance Proteins Publishing Research Research Personnel Resistance Serum Severe Acute Respiratory Syndrome Signal Transduction Site Surface Symptoms T cell therapy Technology Testing Therapeutic Intervention Time Treatment Efficacy Viral Pathogenesis Work arm base chemical stability clinical diagnostics cytokine cytokine release syndrome design diagnosis standard diagnostic assay flexibility fluorescence imaging imaging modality imaging platform improved in vivo in vivo monitoring mechanical properties minimally invasive nanosensors novel nuclease optical imaging photoacoustic imaging predictive marker prevent receptor response scaffold sensor spatiotemporal systemic inflammatory response systems research tool

项目摘要

ABSTRACT Nanosensor technology for continuous monitoring of proteins in vivo would enable researchers to track the dynamics of biomolecule expression as it pertains to disease pathogenesis or predicting therapeutic efficacy, with results available in real-time. An example where this diagnostic ability would be groundbreaking is in the context of understanding cytokine release syndrome (CRS). CRS is a systemic inflammatory response that arises when the immune system is overstimulated, leading to extreme toxic events such as multiple organ dysfunction1. There is now increasing evidence to suggest that the development of severe cases of COVID-19 can be attributed to onset of CRS. It has been revealed that serum levels of cytokines like IFNγ, IL-6, sIL-2Rα, and IL-10 can be significantly elevated in patients with severe CRS, before the apparent onset of severe symptoms. However, the use of cytokines as biomarkers of CRS would require a rapid, minimally invasive diagnostic assay, which is currently unavailable, slowing animal studies of COVID-19/CRS. Recently published research from the Clark laboratory has demonstrated a proof-of-concept DNA-based sensor for minimally invasive detection of IFNγ, one of the cytokines that has been proposed as a biomarker for predicting the potential for onset of severe CRS. This design was inspired by advances in DNA nanotechnology, which enable researchers to create functional nanostructures with site-specific modifications based on the complementary base-pairing rules of DNA. The open or closed state of the sensor could be determined through differential signals as detected with optical imaging. Drawing from recent advances in DNA origami design and stabilization technology, we hypothesize that we can improve on this work and produce a robust platform for optical monitoring of IFNγ in real-time by (1) enhancing the rigidity of our DNA platform and (2) deploying protection strategies to ionically stabilize the construct in biological solutions. This project aims to advance current analytical strategies for immunological diagnostics by providing researchers with a powerful tool to probe biomolecule dynamics toward in vivo use with existing optical imaging platforms. The one-year project will result in a robust tool developed for animal research. The goal will be to commercialize and distribute the sensor for COVID-19 studies, as well as other immune system research.

摘要用于连续监测体内蛋白质的纳米传感器技术将使研究人员能够跟踪蛋白质的变化。生物分子表达的动力学与疾病发病机理或预测治疗效果有关，并实时提供结果。这种诊断能力具有开创性的一个例子是，了解细胞因子释放综合征（CRS）的背景。CRS是一种全身性炎症反应，当免疫系统受到过度刺激时，会出现严重的毒性事件，如多器官功能障碍1.现在有越来越多的证据表明，COVID-19严重病例的发展可以归因于CRS的发作。研究表明，血清中IFNγ、IL-6、sIL-2 R α、而IL-10在重度CRS患者中可显著升高，症状然而，使用细胞因子作为CRS的生物标志物将需要快速、微创的方法来检测CRS。目前尚无法获得的诊断方法，减缓了COVID-19/CRS的动物研究。最近发表克拉克实验室的研究已经证明了一种基于DNA的概念验证传感器， IFNγ的侵入性检测，IFN γ是一种细胞因子，已被提议作为预测肿瘤的生物标志物。严重CRS发作的可能性。这种设计的灵感来自DNA纳米技术的进步，研究人员创建功能性纳米结构与位点特异性修饰的基础上互补的 DNA的碱基配对规则传感器的打开或关闭状态可以通过微分来确定。光学成像检测到的信号。借鉴DNA折纸设计和稳定化的最新进展技术，我们假设我们可以改进这项工作，并产生一个强大的平台，通过（1）增强我们DNA平台的刚性和（2）部署保护措施来实时监测IFNγ 在生物溶液中离子稳定构建体的策略。该项目旨在推进当前的分析免疫学诊断策略，为研究人员提供了探测生物分子的有力工具与现有的光学成像平台的体内使用的动态。为期一年的项目将产生一个强大的为动物研究开发的工具。目标将是商业化和分发COVID-19传感器研究，以及其他免疫系统研究。