Self-organizing synthetic human lungs on microchips to fight infection by RSV
微芯片上的自组织合成人肺可抵抗 RSV 感染
基本信息
- 批准号:10698767
- 负责人:
- 金额:$ 30万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2023
- 资助国家:美国
- 起止时间:2023-05-22 至 2024-04-30
- 项目状态:已结题
- 来源:
- 关键词:2019-nCoVAcute Lung InjuryAirAnti-Infective AgentsBiological AssayCOVID-19 patientCessation of lifeChildClinicalCollectionCoronavirusDevelopmentDiseaseDisease modelDrug KineticsElderlyEpidemicGeometryHumanImageImmunocompromised HostIndividualInfectionIntegration Host FactorsInterphaseLibrariesLife StyleLiquid substanceLungLung infectionsMediatingModelingMolecularOrganPathogenicityPathologyPatientsPharmaceutical PreparationsPhasePhenotypePhysiologicalPhysiologyPneumoniaPropertyPulmonary PathologyRespiratory DiseaseRespiratory Syncytial Virus InfectionsRespiratory syncytial virusRiskStandardizationStimulusStructure of parenchyma of lungTestingTherapeuticTimeTissuesValidationViralViral Respiratory Tract InfectionVirusVirus DiseasesVirus InhibitorsWorkantiviral drug developmentbronchial epitheliumcandidate validationdrug developmentdrug metabolismfightingfollow-upfuture epidemicfuture outbreakhigh throughput screeninghuman diseasehuman pluripotent stem cellin vivoin vivo Modellead optimizationmicrochipmortalitynoveloutbreak controlphase 2 studyphysiologic modelpotency testingrational designrespiratoryrespiratory infection virusrespiratory virusresponsescreeningself organizationsmall moleculetherapeutic candidatetherapeutic developmenttoolviral transmission
项目摘要
Project Summary
RSV is a major global threat that accounts for a significant share of respiratory disease and
mortality among patients at risk. Infection by highly pathogenic RSV results in acute lung injury,
LRTI, and pneumonia-associated complications. As treatments for RSV are very limited in use
and efficacy, the development of physiological models of this disease is key to develop
therapeutics that limit infection by this virus and associated pathology. This proposal will capitalize
on RumiViro’s mini-lung platform that offers inexhaustible access to genetically matched
organotypic human lung tissue to model infection by respiratory viruses. This platform will be
deployed to model RSV infection in physiological lung tissue and identify therapeutics for this
disease at scale. We will first screen a collection of 23,000 compounds of a highly diverse
phenotypic library of bioactive compounds for their ability to mitigate infection by RSV. Hit
candidates will be further validated for their ability to inhibit multiple clinical strains of RSV in mini-
lungs and primary lung tissue ex vivo. This work will have transformative influence for the
subsequent development of therapeutics and will enable further validation of therapeutic
candidates based on drug metabolism, pharmacokinetic analysis, in vivo proof-of-concept and
lead optimization efforts in follow-up Phase 2 studies. This work will provide a highly efficient
framework for the identification and development of RSV therapeutics with the promise of finding
anti-infective therapeutics that mitigate the RSV-induced pathology in patients at risk.
项目总结
项目成果
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