Delivery of chemically modified PNA oligomers
化学修饰的 PNA 寡聚物的递送
基本信息
- 批准号:10006671
- 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:2020
- 资助国家:美国
- 起止时间:2020-03-06 至 2022-02-28
- 项目状态:已结题
- 来源:
- 关键词:AddressAmidesAmino SugarsAminoglycosidesAnimal Disease ModelsAnti-Bacterial AgentsAntibiotic ResistanceAntibioticsAwarenessBacteriaBase PairingBindingBiological AssayBiological AvailabilityBooksBostonCellsChemicalsClinicCommunicable DiseasesComplementComplexCongressesConsultationsCoupledDataDevelopmentDiseaseDrug DesignDrug TargetingDrug resistanceElementsEscherichia coliFaceGram-Negative BacteriaGrowthHealthHigh Pressure Liquid ChromatographyHumanHybridsIn VitroInfectionInstitute of Medicine (U.S.)Legal patentLettersLibrariesLinkLipidsLocalesMembraneMethodsModernizationMusNucleic Acid BindingNucleic AcidsOligonucleotidesOrganic SynthesisPathogenicityPermeabilityPharmaceutical PreparationsPharmacologic SubstancePhasePredispositionPreventionProtein Synthesis InhibitorsRNARNA BindingRNA SequencesReportingRibosomal RNARibosomesSiteSolidSpecificityStructureSurgeonTailTechnologyTherapeuticTimeTissuesToxic effectTranslatingUnited StatesUnited States National Academy of SciencesUnited States National Institutes of HealthWorkantibiotic resistant infectionsantimicrobialantimicrobial drugbasecomparativecostdesigndosagedrug developmentefficacy studyhuman diseasein vivomicrobialmultidisciplinarynew technologynovelnucleic acid deliverypathogenpreventscreeningsmall moleculesuccesstargeted treatmentuptakeweb site
项目摘要
PROJECT SUMMARY
RNA is a validated target for drug design, both as therapeutic and as a target.
Targeting specific RNA, such as rRNA which are involved in proliferation and survival of
bacteria is a promising approach. We are developing fast and low cost methods to
screen sequence-specific small molecules for novel anti-ribosomal activities. We will
construct sequence-specific chemically modified ribosomal targeting oligomers that can
be effectively delivered inside the cell, addressing the key objective of
PAR-17-036 (to generate new technologies and products for delivering nucleic
acids into cells and tissues for the purpose of treatment or prevention of
human disease). Complexes between ribosomal components will be exploited
as targets for small molecule drug libraries that-inactivate the ribosome.
NUBADs unique experimental approaches and technologies will allow us to target
ribosomal regions not previously explored for susceptibility against microbial
targets.
The work proposed here, a multidisciplinary effort encompassing solid-phase
organic synthesis, oligonucleotide delivery, RNA targeted screening, antimicrobial
activity, and in vivo efficacy studies describes the development of sequence-specific cell
permeable binders of rRNA. The success of the proposed work would be a significant
addition to currently available ribosome-specific approaches in drug development. We
propose using a small rRNA target sequences to design conjugates that can be
employed to inhibit microbial growth, opening possibilities for developing sequence-
specific RNA targeted therapeutics.
项目摘要
RNA是药物设计的有效靶点,无论是作为治疗药物还是作为靶点。
靶向特定的RNA,如参与细胞增殖和存活的rRNA,
细菌是一种很有前途的方法。我们正在开发快速和低成本的方法,
筛选新的抗核糖体活性的序列特异性小分子。我们将
构建序列特异性化学修饰的核糖体靶向寡聚体,
在细胞内有效传递,解决以下关键目标:
PAR-17-036(产生用于递送核酸的新技术和产品)
酸进入细胞和组织,以治疗或预防
人类疾病)。核糖体成分之间的复合物将被利用
作为包裹核糖体的小分子药物文库的靶点。
NUBAD独特的实验方法和技术将使我们能够瞄准
核糖体区域以前没有探索过对微生物的敏感性
目标的
这里提出的工作,一个多学科的努力,包括固相
有机合成,寡核苷酸递送,RNA靶向筛选,抗菌
活性和体内功效研究描述了序列特异性细胞
rRNA的渗透性结合物。拟议工作的成功将具有重大意义
除了目前可用的核糖体特异性药物开发方法。我们
我建议使用小rRNA靶序列来设计可以
用于抑制微生物生长,为开发序列提供了可能性-
特异性RNA靶向治疗。
项目成果
期刊论文数量(0)
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{{ truncateString('DEV PRIYA ARYA', 18)}}的其他基金
Aminoglycosides with reduced ototoxicity via miRNA targeting
通过 miRNA 靶向降低耳毒性的氨基糖苷类药物
- 批准号:
9891947 - 财政年份:2019
- 资助金额:
$ 30万 - 项目类别:
Aminoglycosides with reduced ototoxicity via miRNA targeting
通过 miRNA 靶向降低耳毒性的氨基糖苷类药物
- 批准号:
9982540 - 财政年份:2019
- 资助金额:
$ 30万 - 项目类别:
A Rapid assay for RNA targeted drugs: Instrumentation Supplement
RNA 靶向药物的快速检测:仪器补充
- 批准号:
9120576 - 财政年份:2011
- 资助金额:
$ 30万 - 项目类别:
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