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Biostable nucleic acid aptamers for long-duration, in vivo molecular monitoring

用于长时间体内分子监测的生物稳定核酸适体

基本信息

批准号：
10304801
负责人：
Kevin W Plaxco
金额：
$ 20.89万
依托单位：
UNIVERSITY OF CALIFORNIA SANTA BARBARA
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-06-15 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10304801
关键词：
Adult Respiratory Distress Syndrome Aminoglycosides Animal Model Antibiotics Binding Biological Markers Biotechnology Blood Brain COVID-19 Caliber Chemicals Clinical Communicable Diseases Creatinine Development Diabetes Mellitus Diagnosis Diagnostic Disease Dose Dose-Limiting Drug Kinetics Electrodes Electron Transport Elements Exhibits Feedback Glucose Goals Health Health Status Hormones Hour In Situ In Vitro Infection Measurable Measurement Measures Medical Research Molecular Monitor Muscle Nucleic Acids Oligonucleotides Outcome Output Oxidation-Reduction Patients Performance Pharmaceutical Preparations Preclinical Testing Problem Solving Process Rattus Renal function Reporter Reporting Research Resistance Safety Sensitivity and Specificity Sepsis Signal Transduction Site Solid Specificity Surface Technology Therapeutic Therapeutic Index Time Tissues Tobramycin Toxic effect Vancomycin Vertebral column Whole Blood Widow Work aptamer awake base clinical practice clinically actionable clinically relevant cytokine diagnostic biomarker drug efficacy falls glucose monitor improved in vitro testing in vivo in vivo evaluation in vivo monitoring innovation minimally invasive monolayer oxidation precision drugs protein biomarkers real time monitoring research clinical testing sensor temporal measurement treatment duration

项目摘要

Summary. Electrochemical, aptamer-based (EAB) sensors are a minimally invasive technology already shown to support seconds-resolved, real-time, in vivo molecular measurements irrespective of the chemical reactivity of its targets. That is, EAB sensors are the only real-time molecular measurement technology that is simultaneously (1) generalizable to drugs and biomarkers and (2) demonstrated to work in situ in the body. In support of these claims, as preliminary results we have reported the first ever seconds- (and even sub-second) resolved, in-vivo measurements of multiple drugs and protein biomarkers. These measurements, which employ 75-µm-diameter sensors placed in situ in the blood (jugular) and tissues (brain, muscle) of awake, freely moving rats, achieve clinically relevant accuracy, precision and specificity over the course of hours. A remaining technological limitation, however, still precludes the further clinical testing of EAB sensors: after more than after ~5 h in vivo, aptamer degradation begins to reduce EAB precision significantly. The R21 project described here is focused on solving this problem. Specifically, here we propose the introduction of degradation-resistant, non-natural XNA aptamers into the EAB platform as a means achieving multi-day in vivo molecular measurements. Successful conclusion of this work would set the stage for R01-scale projects aimed at ascertaining the clinical value of long-duration EAB measurements in, for example, the feedback-controlled delivery of narrow-therapeutic-index antibiotics over multi-day treatment courses and the real-time monitoring of diagnostic cytokines in the ICU over the multi-day clinical course of infections, such as in sepsis and COVID-19.

总结。基于适配体（EAB）的电化学传感器是一种微创技术