An early-intervention gene-editing therapeutic for Pulmonary Arterial Hypertension
An early-intervention gene-editing therapeutic for Pulmonary Arterial Hypertension
批准号:
10603715
负责人:
Vinod Jaskula-Ranga
金额:
$35.0万
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
项目状态:
已结题
起止时间:
2023-09-01 至 2024-08-31
关键词:
AgreementAllelesAltitudeAnimal ModelBenchmarkingBiological AssayCell LineCessation of lifeClinicalClustered Regularly Interspaced Short Palindromic RepeatsDependovirusDiagnosisDiseaseEarly InterventionEndothelial CellsEndotheliumEtiologyExposure toGene DeliveryGenesHumanHuman GenomeHuman RightsHypoxiaHypoxia Inducible FactorHypoxia-Inducible Factor PathwayIn VitroInternationalInterventionLeadLegal patentLicensingLungLung diseasesMediatorMedicineModelingMorbidity - disease rateMusOutcomeOxygenPathologicPathway interactionsPatientsPharmaceutical PreparationsPhasePhysiologic intraventricular pressurePopulationPre-Clinical ModelProteinsPulmonary HypertensionPulmonary arterial remodelingResearch PersonnelRight Ventricular HypertrophyRightsRodent ModelRoleSiteSystemTechnologyTertiary Protein StructureTestingTherapeuticToxicologyTranscriptTransfectionTropismValidationVariantVascular remodelingVirusclinically relevantcommercializationconditional knockoutcurative treatmentsdelivery vehiclegenetic payloadgenome-wide analysisin vitro Assayin vivoin vivo Modelinnovationmortalitynovel therapeutic interventionnovel therapeuticspharmacologicprematurepromoterprophylacticpublic health relevancepulmonary arterial hypertensionpulmonary arterial pressurepulmonary artery endothelial cellpulmonary vascular disorderrepairedresponseright ventricular failuresmall molecule inhibitortherapeutic developmenttherapeutic genome editingtimeline
中文摘要
项目总结/文摘
英文摘要
PROJECT SUMMARY/ABSTRACT
Pulmonary arterial hypertension (PAH) is a rapidly progressing pulmonary vascular disease that leads to right
heart failure and premature death. The hallmark features of PAH are increased pulmonary arterial pressure,
vascular remodeling, and right ventricle hypertrophy. There are no curative treatments for PAH and
approximately 1,000 new cases of PAH are diagnosed in the U.S. each year with a median survival of 6 years.
Novel therapies are urgently needed. Hypoxia-inducible factors (HIF) are critical mediators of the oxygen sensing
and adaptive pathways, and strong evidence supports HIF-2α pathway activation in PAH. Patients with PAH
have elevated HIF-2α levels, and pathway activation is well supported by preclinical models. Conversely,
reduced pathway activity through either pharmacologic inhibition or conditional knockouts is protective in multiple
animal models. A role for HIF-2α is further supported by genome-wide studies of high-altitude populations with
low pulmonary arterial pressure that carry HIF-2α variants with reduced activity. We hypothesize that gene-
editing represents a novel therapeutic approach to suppress HIF-2α pathway activation that underlies PAH
etiology. Hunterian's proprietary technology enables packaging of CRISPR components into a single AAV virus.
In this Phase I, we develop a gene-editing approach to target HIF-2α activation.
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会议论文
Gene Therapy for Cystic Fibrosis Using Novel Compact Promoters
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批准号:10547419
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项目类别:
-
资助金额:$32.0万
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财政年份:2022
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负责人:Vinod Jaskula-Ranga
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依托单位:
海外基金