Molecular Therapies for Cystic Fibrosis Lung Disease
囊性纤维化肺病的分子疗法
基本信息
- 批准号:10470331
- 负责人:
- 金额:$ 231.16万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-01 至 2025-07-31
- 项目状态:未结题
- 来源:
- 关键词:AddressAdenineAirway DiseaseAmphotericin BAnimal ModelAnionsApicalBacteriaBicarbonatesBiologyCellsClinical ResearchClustered Regularly Interspaced Short Palindromic RepeatsComplementCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDNADataDeaminaseDefectDevelopmentDiseaseEpithelial CellsFamily suidaeFerretsFormulationGenetic DiseasesGenetic EngineeringGoalsGuide RNAHost DefenseHumanIn VitroInfrastructureIon ChannelKnowledgeLifeLungLung diseasesMediatingMissense MutationModelingMolecularMorbidity - disease rateMucociliary ClearanceMutationNatural ImmunityNebulizerNucleotidesPathogenesisPeptidesPersonsPreventionPropertyProteinsPulmonary Cystic FibrosisRNA SplicingRecordsResearchResearch PersonnelRespiratory FailureRibonucleoproteinsRoleServicesSiteSurfaceTechniquesTestingVariantWorkadeno-associated viral vectorairway epitheliumairway obstructionairway surface liquidantimicrobialbase editingbase editorcell typecellular targetingcystic fibrosis airwaycystic fibrosis airway epitheliagain of functiongene discoverygene repairgene replacementgene therapyin vivoinnovationloss of functionmortalitynovel therapeutic interventionnovel therapeuticsnull mutationoverexpressionpreventprogenitorprogramsprotein functionrecurrent infectionrepairedsmall moleculetool
项目摘要
OVERALL COMPONENT
PROJECT SUMMARY
Cystic fibrosis (CF) is a common life-shortening genetic disease that causes progressive lung failure due
to recurrent infections and airway obstruction. While our knowledge of CFTR function has advanced
greatly in the 30 years since the discovery of the gene, treatments for the disease remain suboptimal and
CF remains progressive and fatal. Advances with small molecule CFTR modulator therapies have
helped restore protein function for many mutations, but approximately 10% of people with CF have not
benefited from these strategies, including people with nonsense and splicing mutations. The central
theme of this proposal is developing new molecular therapies to prevent or treat CF lung disease.
The goal of our three projects and four cores is to exploit the power of our in vitro and animal models to
address questions fundamental to lung disease pathogenesis and to use this knowledge to inform new
therapeutic strategies to complement CF defects, including gene repair and the addition of a small
molecule that forms anion channels. The three closely interrelated Projects will work together to
accomplish the following goals: 1) To restore CFTR function using targeted single nucleotide
editing. We hypothesize that cells in the surface airway epithelium, including those with progenitor
capacity, can be targeted to repair CFTR mutations using base editing. 2) To understand the
mechanisms of amphotericin B (AmB)-induced anion secretion in airway epithelia and to test the
hypothesis that AmB can restore CF host defenses in vivo. AmB is a small molecule that forms
anion channels. 3) To determine how CFTR expression in pulmonary ionocytes and ciliated cells
regulates properties of the airway surface liquid that are crucial for clearance and innate
immunity. The development of effective gene therapies for cystic fibrosis lung disease must be guided
by a clear understanding of pathophysiologic mechanisms of disease and the relevant cellular targets for
CFTR gene replacement or editing.
The Project Leaders and their teams have outstanding track records of collaborative CF research, and
here they sharpen their focus to a common goal. Their highly creative research is supported by four
cores that provide innovative infrastructure and services. Through these studies we hope to accelerate
the development of new therapeutics for CF lung disease.
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整体组件
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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PAUL B MCCRAY其他文献
PAUL B MCCRAY的其他文献
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{{ truncateString('PAUL B MCCRAY', 18)}}的其他基金
Molecular Therapies for Cystic Fibrosis Lung Disease
囊性纤维化肺病的分子疗法
- 批准号:
10677580 - 财政年份:2020
- 资助金额:
$ 231.16万 - 项目类别:
Gene Editing Strategies to Correct CFTR Mutations
纠正 CFTR 突变的基因编辑策略
- 批准号:
10024666 - 财政年份:2020
- 资助金额:
$ 231.16万 - 项目类别:
Gene Editing Strategies to Correct CFTR Mutations
纠正 CFTR 突变的基因编辑策略
- 批准号:
10677600 - 财政年份:2020
- 资助金额:
$ 231.16万 - 项目类别:
Molecular Therapies for Cystic Fibrosis Lung Disease
囊性纤维化肺病的分子疗法
- 批准号:
10024661 - 财政年份:2020
- 资助金额:
$ 231.16万 - 项目类别:
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