Engineering non-proliferating-but-active (NPBA) probiotic for breast-cancer gene therapy
用于乳腺癌基因治疗的工程非增殖但有活性(NPBA)益生菌
基本信息
- 批准号:10350147
- 负责人:
- 金额:$ 20.66万
- 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:2021-12-02 至 2023-11-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAntibioticsAttenuatedAutolysisBRCA1 geneBacteriaBreastBreast Cancer CellBreast Cancer ModelBreast Cancer TreatmentBreast Cancer cell lineBreast Cancer geneBreast Cancer therapyCD47 geneCell LineCell membraneCellsClustered Regularly Interspaced Short Palindromic RepeatsCytosolDNADNA deliveryDataDevelopmentDiseaseDrug Delivery SystemsDrug resistanceDuct (organ) structureERBB2 geneEffectivenessEngineeringEnvironmentEscherichia coliEssential GenesEstrogen AntagonistsFaceFoundationsFutureGene AmplificationGene DeliveryGene ExpressionGenesGrowthHeelHydrogelsInfectionInvadedLabelLeadListeria monocytogenesMammalian CellMeasuresMembraneMetabolismMethodsMolecularMolecular TargetMonoclonal AntibodiesOncogenicOrganPIK3CA genePathway interactionsPatientsPenetrationPharmaceutical PreparationsPhenotypeProbioticsProteinsProteomeRNARecombinantsResearchResistanceSiteSolid NeoplasmStressSystemSystemic TherapyT cell responseT-LymphocyteTP53 geneTestingTherapeuticTissuesTreatment EfficacyWorkYersinia pestisantagonistanti-canceraqueousbiomaterial compatibilitycancer cellcancer immunotherapycancer therapycrosslinkcytotoxicdelivery vehicledesigndrug developmenteffective therapygene repairgene therapygenome editingin vivoinformation processinginnovationloss of function mutationmalignant breast neoplasmnanobodiesnovel strategiesnovel therapeuticspublic health relevanceside effecttherapeutic proteintooltumor
项目摘要
PROJECT SUMMARY
Engineering non-proliferating-but-active (NPBA) probiotic for breast-cancer gene therapy
A major breast-cancer treatment challenge is the debilitating effects of systemic therapies. To create more
tolerable and effective therapies against breast cancer, considerable effort is being directed to using CRISPR-
Cas to target the molecular origins of the disease. However, current methods face multiple challenges in
delivering CRISPR-Cas to breast cancer cells, including low penetration of solid tumors, low delivery amount,
and small size of CRISPR-Cas. To address the challenges, we will engineer a new kind of CRISPR-Cas delivery
vehicle for breast cancer cells using non-proliferating-but-active (NPBA) probiotic. Our preliminary work
demonstrates that the NPBA probiotic conduct metabolism, move in aqueous environments, and does not
proliferate. We ultimately envisage that the NPBA probiotic can be introduced into the breast ducts or tumors to
migrate towards cancer cells and then deliver a CRISPR-Cas construct that targets specific oncogenic
mechanisms. Hence, this proposal aims to engineer these NPBA probiotic to deliver genes or proteins to breast
cancer cells. Our team will leverage expertise in gene expression control, bacterial information processing,
molecular tools, and breast cancer models. We will pursue two parallel aims that correspond to the engineering
and testing of the NPBA Escherichia coli Nissle 1917. 1) Enable NPBA probiotics to invade mammalian cells
before delivering CRISPR-Cas. This aim will establish the basic CRISPR-Cas-delivery function of the NPBA
probiotics. 2) Enhance the invasion and CRISPR-Cas delivery efficacy of the NPBA probiotic in silencing the
ErbB2 oncogene of breast cancer cells. This project will create a new paradigm that uses non-proliferating-but-
active probiotics for effective and specific delivery of CRISPR-Cas to cancer cells. Our work will also form the
foundation for using the NPBA probiotics to target various oncogenic and proliferative pathways of cancer cells.
Future work may also investigate any dispersion of the NPBA probiotics into the surrounding tissues and
throughout the host.
项目总结
项目成果
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{{ truncateString('RUSSELL C HOVEY', 18)}}的其他基金
Engineering non-proliferating-but-active (NPBA) probiotic for breast-cancer gene therapy
用于乳腺癌基因治疗的工程非增殖但有活性(NPBA)益生菌
- 批准号:
10533816 - 财政年份:2021
- 资助金额:
$ 20.66万 - 项目类别:
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