Therapy for drug resistant influenza strains by nucleic acid targeting of respiratory airways
核酸靶向呼吸道治疗耐药流感病毒株
基本信息
- 批准号:9406008
- 负责人:
- 金额:$ 4.99万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-07-02 至 2018-06-30
- 项目状态:已结题
- 来源:
- 关键词:Anti-Bacterial AgentsAntiviral AgentsAntiviral ResponseAntiviral TherapyBacterial PneumoniaBenignCardiovascular DiseasesCationsCellsCessation of lifeChargeChitosanChronicComorbidityComplexCytosolDiseaseDrug UtilizationDrug resistanceEbola virusEffectivenessElectrostaticsEpidemicFerretsFormulationGenesGeneticGenetic TranscriptionGoalsGuidelinesHospitalizationHumanIRF3 geneImmuneImmune responseIn VitroIncidenceIndividualInfectionInfluenzaInfluenza A Virus, H1N1 SubtypeInfluenza A Virus, H5N1 SubtypeInfluenza A virusInnate Immune ResponseInterferon Type IInterferonsLaboratoriesLigandsLung diseasesMessenger RNAMorbidity - disease rateMusNonstructural ProteinNucleic AcidsPathogenicityPatientsPhasePhase I Clinical TrialsPolymersPopulationProductionRNARNA InterferenceResistanceRiskSafetySecondary toSignal TransductionSmall Business Technology Transfer ResearchStressStructure of respiratory epitheliumSurfaceTLR3 geneTRIM25 geneTestingTherapeuticTimeToxic effectTreatment EfficacyUbiquitinationVaccinesVentViralVirulenceVirulence FactorsVirulentVirus DiseasesVirus Replicationanti-influenzabiomaterial compatibilitycytokinedesigndrug resistant influenzafluimprovedin vivokillingsknock-downlung injurymRNA Transcript Degradationmortalitynanonanoparticlenovelnovel therapeuticspandemic diseaseresistant strainrespiratoryresponsesensorsmall hairpin RNAsuccesstherapeutic genetransmission processtreatment strategyviral RNA
项目摘要
PROJECT SUMMARY
Antiviral drugs are a crucial countermeasure for influenza A virus (IAV), particularly in circumstances of
increased IAV incidence or if a vaccine is unavailable (e.g., virulent H5N1 IAV). However, the emergence of IAV
strains that are resistant to current antivirals1-6 (H5N1) underscores the need for new treatment strategies,
particularly those that modify the host response. IAVs infect 5-20% of the US population with >200,000
hospitalizations and ~40,000 deaths annually. Morbidity and mortality are secondary to an intense systemic
stress to the antiviral immune response particularly in those individuals with co-morbidities (i.e., chronic
respiratory and cardiovascular diseases). Additionally, endemic IAV strains from other species (e.g., H5N1) can
kill healthy individuals by a “cytokine storm”. The emergence of pandemic strains is inevitable, as seen most
recently with 2009 H1N1. Moreover, IAV’s ability to rapidly acquire increased virulence and efficient human-to-
human transmission through genetic shift is a constant threat to the global population, and benign strains may
rapidly evolve and cause severe morbidity and mortality. This application proposes to develop for use in patients
a novel therapeutic gene knockdown strategy localized to respiratory epithelium by employing nanoplexes, an
electrostatic complex of cationic polymers and anionic nucleic acids. Our preliminary findings have demonstrated
that this antiviral therapy, inhibits IAV replication, decreases IAV induced lung injury and improves antibacterial
host responses. This Phase I STTR application will optimize the fabrication and delivery of the nanoplexes and
establish its in vitro efficacy (with respect to antiviral and IFN I stimulating activity) and toxicity. The subsequent
Phase II STTR application will determine its in vivo efficacy and toxicity in mice and ferrets utilizing drug-resistant
laboratory, epidemic, pandemic, and pathogenic strains.
项目总结
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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Charles Houston Jones其他文献
Charles Houston Jones的其他文献
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{{ truncateString('Charles Houston Jones', 18)}}的其他基金
DEVELOPMENT OF A LIPOSOMAL PNEUMOCOCCAL VACCINE FOR CLINICAL READINESS
开发用于临床准备的脂质体肺炎球菌疫苗
- 批准号:
10373030 - 财政年份:2020
- 资助金额:
$ 4.99万 - 项目类别:
DEVELOPMENT OF A LIPOSOMAL PNEUMOCOCCAL VACCINE FOR CLINICAL READINESS
开发用于临床准备的脂质体肺炎球菌疫苗
- 批准号:
10010219 - 财政年份:2020
- 资助金额:
$ 4.99万 - 项目类别:
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