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:10430240
- 负责人:
- 金额:$ 23.4万
- 依托单位:
- 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:
- 关键词:Acute Respiratory Distress SyndromeAminoglycosidesAnimal ModelAntibioticsBindingBiological MarkersBiotechnologyBloodBrainCOVID-19ChemicalsClinicalCommunicable DiseasesContinuous Glucose MonitorCreatinineDevelopmentDiabetes MellitusDiagnosisDiagnosticDiameterDiseaseDoseDose LimitingDrug KineticsElectrodesElectron TransportElementsEngineeringExhibitsFeedbackGlucoseGoalsHealthHealth StatusHormonesHourIn SituIn VitroInfectionMeasurableMeasurementMeasuresMedical ResearchMolecularMonitorMuscleNucleic AcidsOligonucleotidesOutcomeOutputOxidation-ReductionPatientsPerformancePharmaceutical PreparationsPreclinical TestingProcessRattusRenal functionReporterReportingResearchResistanceSafetySepsisSignal TransductionSiteSolidSpecificitySurfaceTechnologyTherapeuticTherapeutic IndexTimeTissuesTobramycinToxic effectVancomycinVertebral columnWhole BloodWidowWidowhoodWorkaptamerawakeclinical practiceclinically actionableclinically relevantcytokinediagnostic biomarkerdrug efficacyfabricationfallsimprovedin vitro testingin vivoin vivo evaluationin vivo monitoringinnovationmeterminimally invasivemonolayeroxidationprecision drugsprotein biomarkersreal time monitoringresearch clinical testingself assemblysensortemporal measurementtreatment 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。基于电化学适配子(EAB)的传感器是一种已经展示的微创技术
支持秒分辨率的、实时的在体分子测量,而与化学反应无关
它的目标。也就是说,EAB传感器是唯一的实时分子测量技术,
同时(1)可推广到药物和生物标志物,以及(2)被证明在体内原位起作用。在……里面
支持这些主张,作为初步结果,我们已经报告了有史以来的第一秒--甚至亚秒)
多种药物和蛋白质生物标志物的体内可分辨测量。这些衡量标准采用了
直径75微米的传感器原位放置在清醒、自由活动的血液(颈静脉)和组织(脑、肌肉)中
大鼠,在数小时内达到临床相关的准确性、精密度和特异性。剩余的
然而,技术限制仍然阻碍了EAB传感器的进一步临床测试:在此之后
体内5h内,适体降解开始显著降低EAB的精密度。这里介绍的R21项目
致力于解决这个问题。具体地说,我们在这里建议引入抗降解性,
以非天然XNA适配子进入EAB平台为手段实现体内多日分子
测量。这项工作的圆满完成将为旨在实现以下目标的R01规模项目奠定基础
确定长期EAB测量的临床价值,例如,反馈控制
在多天疗程中提供窄治疗指数抗生素,并实时监测
在感染的多天临床病程中,ICU中的诊断细胞因子,例如在脓毒症和新冠肺炎中。
项目成果
期刊论文数量(0)
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Kevin W Plaxco其他文献
Kevin W Plaxco的其他文献
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{{ truncateString('Kevin W Plaxco', 18)}}的其他基金
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
- 批准号:
10304801 - 财政年份:2021
- 资助金额:
$ 23.4万 - 项目类别:
Feedback controlled, ultra-high-precision drug delivery
反馈控制的超高精度药物输送
- 批准号:
10084266 - 财政年份:2019
- 资助金额:
$ 23.4万 - 项目类别:
Feedback controlled, ultra-high-precision drug delivery
反馈控制的超高精度药物输送
- 批准号:
10321612 - 财政年份:2019
- 资助金额:
$ 23.4万 - 项目类别:
Feedback controlled, ultra-high-precision drug delivery
反馈控制的超高精度药物输送
- 批准号:
9761770 - 财政年份:2019
- 资助金额:
$ 23.4万 - 项目类别:
Bio-electrochemical detectors for in vivo continuous monitoring
用于体内连续监测的生物电化学检测器
- 批准号:
9238429 - 财政年份:2017
- 资助金额:
$ 23.4万 - 项目类别:
Bio-electrochemical detectors for in vivo continuous monitoring
用于体内连续监测的生物电化学检测器
- 批准号:
9551624 - 财政年份:2017
- 资助金额:
$ 23.4万 - 项目类别:
A new approach to quantitative, point-of-care serology
定量、护理点血清学的新方法
- 批准号:
9306748 - 财政年份:2014
- 资助金额:
$ 23.4万 - 项目类别:
A new tool for measuring surface-biomolecule interactions
测量表面生物分子相互作用的新工具
- 批准号:
8662567 - 财政年份:2014
- 资助金额:
$ 23.4万 - 项目类别:
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