Delivery of chemically modified PNA oligomers
Delivery of chemically modified PNA oligomers
批准号:
10006671
负责人:
DEV PRIYA ARYA
金额:
$30.0万
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
项目状态:
已结题
起止时间:
2020-03-06 至 2022-02-28
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
中文摘要
项目总结
无论是作为治疗还是作为靶点,RNA都是药物设计的有效靶点。
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来
筛选序列特异的小分子以获得新的抗核糖体活性。我们会
构建序列特异的化学修饰的核糖体靶向寡聚体,能够
在细胞内有效传递,满足以下关键目标
PAR-17-036(产生用于交付核的新技术和产品
酸进入细胞和组织,用于治疗或预防
人类疾病)。核糖体成分之间的复合体将被开发
作为使核糖体失活的小分子药物库的靶标。
NUBADs独特的实验方法和技术将使我们能够
核糖体区域以前未被发现对微生物的敏感性
目标。
这里提出的工作,一项包括固相的多学科努力
有机合成、寡核苷酸递送、RNA靶向筛选、抗菌剂
活性和体内药效研究描述了序列特异性细胞的发育
RRNA的可渗透结合体。拟议工作的成功将是一个重要的
除了目前药物开发中可用的核糖体特异性方法之外。我们
建议使用小的rRNA靶序列来设计可以
用来抑制微生物生长,为开发序列打开了可能性-
特定的RNA靶向疗法。
英文摘要
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.
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会议论文
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海外基金