Maximizing small RNA delivery with signaling pepitdes
通过信号肽最大化小 RNA 递送
基本信息
- 批准号:9145216
- 负责人:
- 金额:$ 23.59万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-09-16 至 2018-06-30
- 项目状态:已结题
- 来源:
- 关键词:Adverse effectsBacteriophagesBiocompatible MaterialsBiological AssayBiological AvailabilityBiomedical EngineeringCarrier ProteinsCell SeparationCellsCellular biologyChargeClinicalCodeCoupledCytoplasmDataDevelopmentDoseDrug Delivery SystemsFormulationFutureGene SilencingGoalsHealthImmuneLeadLibrariesMeasuresMediatingMicroRNAsMolecularMultivesicular BodyNucleic AcidsParticle SizeParticulatePeptide Signal SequencesPeptidesProcessPropertyProtein EngineeringProteinsRNARNA Recognition MotifRNA-Induced Silencing ComplexResearchSafetySignal TransductionSiteSmall Interfering RNASmall RNASorting - Cell MovementStagingSurfaceTechniquesTestingTherapeuticTreatment EfficacyVirusbasecancer cellcell typedesignhealth applicationhuman diseaseimprovedin vivointerdisciplinary approachnanocarriernanotherapeuticnovelprotein aminoacid sequencereceptorscreeningtrafficking
项目摘要
DESCRIPTION (provided by applicant): The objective of this mechanism-based research is to devise safe and efficient protein particulate nanocarriers (PPC) for small RNA delivery. To accomplish this, we plan to exploit the intracellular trafficking machinery to direct the delivery f small RNAs to their site of action while maximizing small RNA delivery. Small RNAs are used in a range of health applications. However, their potential has yet to be fully realized. This is largely due to inefficient delivery: only 1-2% of small RNAs reach the RNA-induced silencing complex (RISC): the site of action using conventional techniques. Small RNA delivery is a multistep process in which inefficiencies at any stage can compromise the efficacy of gene silencing. In particular, the intracellular fate of synthetic carriers is not well understood and tus poorly controlled. Recent studies indicate that active RISCs are functionally and physically coupled to MVBs and are not free in the cytoplasm as previously thought. Thus, we hypothesize that the effect of small RNA delivery can be significantly increased by actively targeting MVBs. We propose the design of PPCs containing signaling moieties that are recognized by the cell sorting machinery and that serve as "molecular zip codes" for the directed transport of small RNAs to the RISC. This could ultimately lead to enhanced gene silencing. This strategy could improve RNA-based therapy by allowing for the administration of lower doses of therapeutics, thereby reducing side effects and improving safety profiles.
描述(由申请人提供):这项基于机制的研究的目的是设计用于小RNA递送的安全有效的蛋白质颗粒纳米载体(PPC)。为了实现这一点,我们计划利用细胞内运输机制来引导小RNA递送到它们的作用位点,同时最大化小RNA递送。小RNA用于一系列健康应用。然而,它们的潜力尚未充分发挥。这在很大程度上是由于低效率的递送:只有1-2%的小RNA到达RNA诱导沉默复合物(RISC):使用常规技术的作用位点。小RNA递送是一个多步骤的过程,其中任何阶段的效率低下都可能损害基因沉默的功效。特别是,合成载体的细胞内命运没有得到很好的理解,并且我们控制得很差。最近的研究表明,活性RISC在功能上和物理上与MVB偶联,并且不像以前认为的那样游离在细胞质中。因此,我们假设小RNA递送的效果可以通过主动靶向MVB而显著增加。我们提出了PPC的设计含有信号传导部分,被细胞分选机识别,并作为“分子邮政编码”的小RNA的直接运输到RISC。这可能最终导致增强的基因沉默。这种策略可以通过允许给予较低剂量的治疗剂来改善基于RNA的治疗,从而减少副作用并改善安全性。
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(1)
The Phenotypic Effects of Exosomes Secreted from Distinct Cellular Sources: a Comparative Study Based on miRNA Composition.
- DOI:10.1208/s12248-018-0227-4
- 发表时间:2018-04-30
- 期刊:
- 影响因子:0
- 作者:Ferguson S;Kim S;Lee C;Deci M;Nguyen J
- 通讯作者:Nguyen J
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Juliane Nguyen其他文献
Juliane Nguyen的其他文献
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{{ truncateString('Juliane Nguyen', 18)}}的其他基金
Developing genetically encodable probes for multimodal tracking of exosomal RNA cargo
开发用于外泌体 RNA 货物多模式追踪的基因可编码探针
- 批准号:
10681827 - 财政年份:2023
- 资助金额:
$ 23.59万 - 项目类别:
Engineering a cross-linked cellular network for cardiac repair
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10539723 - 财政年份:2022
- 资助金额:
$ 23.59万 - 项目类别:
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10380283 - 财政年份:2021
- 资助金额:
$ 23.59万 - 项目类别:
Polarizing Macrophages to Tumor Suppressors by Blocking Multiple CCR2 Chemokine Receptor Epitopes
通过阻断多个 CCR2 趋化因子受体表位将巨噬细胞极化为肿瘤抑制因子
- 批准号:
10328882 - 财政年份:2020
- 资助金额:
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Polarizing Macrophages to Tumor Suppressors by Blocking Multiple CCR2 Chemokine Receptor Epitopes
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9973323 - 财政年份:2020
- 资助金额:
$ 23.59万 - 项目类别:
Polarizing Macrophages to Tumor Suppressors by Blocking Multiple CCR2 Chemokine Receptor Epitopes
通过阻断多个 CCR2 趋化因子受体表位将巨噬细胞极化为肿瘤抑制因子
- 批准号:
10737843 - 财政年份:2020
- 资助金额:
$ 23.59万 - 项目类别:
Polarizing Macrophages to Tumor Suppressors by Blocking Multiple CCR2 Chemokine Receptor Epitopes
通过阻断多个 CCR2 趋化因子受体表位将巨噬细胞极化为肿瘤抑制因子
- 批准号:
10524148 - 财政年份:2020
- 资助金额:
$ 23.59万 - 项目类别:
Polarizing Macrophages to Tumor Suppressors by Blocking Multiple CCR2 Chemokine Receptor Epitopes
通过阻断多个 CCR2 趋化因子受体表位将巨噬细胞极化为肿瘤抑制因子
- 批准号:
10559551 - 财政年份:2020
- 资助金额:
$ 23.59万 - 项目类别:
Self-replicating RNA-nanoplexes for programming monocytes to regenerate the heart
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- 批准号:
8968584 - 财政年份:2015
- 资助金额:
$ 23.59万 - 项目类别:
Self-replicating RNA-nanoplexes for programming monocytes to regenerate the heart
用于编程单核细胞以再生心脏的自我复制RNA纳米复合物
- 批准号:
9105404 - 财政年份:2015
- 资助金额:
$ 23.59万 - 项目类别:
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