Development of Fluorogenic Aptamers for Detection and Deactivation of Erbb Receptors using Bifacial PNA

使用双面 PNA 开发用于检测和灭活 Erbb 受体的荧光适体

基本信息

  • 批准号:
    9287930
  • 负责人:
  • 金额:
    $ 28.44万
  • 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:
    2015-06-01 至 2020-05-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): A long term goal in our lab is to determine the structure-function scope of bPNA. The objective of this application is to use bPNA to produce fluorogenic aptamers that are function as theranostic tools for study and treatment of HER-amplified cancer. The central hypothesis of this application is that bPNA hybridization with nucleic acid libraries can be used to integrate fluorogen-photosensitizers into affinity selection such that the fluorogen is a component of the recognition site that makes close contact with the ERBB receptor. Target binding thus activates fluorescence and exposes the aptagenic site to maximum damage by fluorogen-produced reactive oxygen species. Our rationale for this hypothesis is the finding that bPNA triplex hybridization can fluorescently label DNA and RNA aptamers. Our independent efforts are supported by the shared resources and expertise of the Center for RNA Biology at the Ohio State University as well as collaborators in clinical investigation of HER+ breast cancer, ERBB receptor biochemistry, SELEX, photoimmunotherapy on ERBB-dysregulated cancer and photo physical methods. These factors combine to create a setting conducive to the successful completion of the proposed investigations. The proposed research is creative and original because a new general method is described using bPNA hybrid structures that will seamlessly incorporate non-native groups (fluorogens) into affinity selection. This will allow selection for artificial functional groups atthe aptamer-target recognition interface. The bPNA-aptamer hybrid structures offer transformative advantages not previously known. This creative, original approach will yield the following expected outcomes: 1) a widely applicable procedure for inclusion of prosthetic groups in SELEX; 2) fluorogenic reporters of HER2, HER3 and heterodimer status, as well as a general protocol to report on any aptagenic site; 3) aptamer- directed inactivation of HER2 and HER3 in vitro and in cell culture. The proposed research will yield theranostic fluorogenic aptamers for diagnosis and treatment of HER-amplified breast cancer as well as establish a general protocol for aptamer-directed biosensors and photodynamic therapeutic reagents.
 描述(由申请人提供):我们实验室的长期目标是确定 bPNA 的结构功能范围。该应用的目的是使用 bPNA 生产荧光适体,作为研究和治疗 HER 扩增癌症的治疗诊断工具。该应用的中心假设是,bPNA 与核酸文库的杂交可用于将荧光光敏剂整合到亲和选择中,使得荧光基成为与 ERBB 受体紧密接触的识别位点的组成部分。因此,靶标结合激活荧光并使适体位点受到荧光产生的活性氧的最大损害。我们提出这一假设的理由是发现 bPNA 三重杂交可以荧光标记 DNA 和 RNA 适体。我们的独立努力得到了俄亥俄州立大学 RNA 生物学中心的共享资源和专业知识以及 HER+ 乳腺癌临床研究、ERBB 受体生物化学、SELEX、ERBB 失调癌症的光免疫疗法和光物理方法方面的合作者的支持。这些因素结合起来创造了有利于成功完成拟议调查的环境。所提出的研究具有创造性和原创性,因为使用 bPNA 混合结构描述了一种新的通用方法,该方法将无缝地将非天然基团(荧光团)纳入亲和力选择中。这将允许在适体-靶标识别界面处选择人工官能团。 bPNA-适体混合结构提供了以前未知的变革优势。这种创造性、原创性的方法将产生以下预期成果:1)将假肢组纳入 SELEX 的广泛适用程序; 2) HER2、HER3 和异二聚体状态的荧光报告基因,以及报告任何适体位点的通用方案; 3)体外和细胞培养物中适体引导的HER2和HER3失活。拟议的研究将产生用于诊断和治疗 HER 扩增乳腺癌的治疗诊断荧光适体,并建立适体导向的生物传感器和光动力治疗试剂的通用方案。

项目成果

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Dennis Bong其他文献

Dennis Bong的其他文献

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{{ truncateString('Dennis Bong', 18)}}的其他基金

URIL tags for intracellular RNA tracking and RNP proximity labeling
用于细胞内 RNA 追踪和 RNP 邻近标记的 URIL 标签
  • 批准号:
    10738661
  • 财政年份:
    2023
  • 资助金额:
    $ 28.44万
  • 项目类别:
Synthetic strategies for non-canonical hybridization to structural motifs in RNA
RNA 结构基序非规范杂交的合成策略
  • 批准号:
    10278692
  • 财政年份:
    2021
  • 资助金额:
    $ 28.44万
  • 项目类别:
Synthetic strategies for non-canonical hybridization to structural motifs in RNA
RNA 结构基序非规范杂交的合成策略
  • 批准号:
    10478071
  • 财政年份:
    2021
  • 资助金额:
    $ 28.44万
  • 项目类别:
Synthetic strategies for non-canonical hybridization to structural motifs in RNA
RNA 结构基序非规范杂交的合成策略
  • 批准号:
    10689745
  • 财政年份:
    2021
  • 资助金额:
    $ 28.44万
  • 项目类别:
Development of Fluorogenic Aptamers for Detection and Deactivation of Erbb Receptors using Bifacial PNA
使用双面 PNA 开发用于检测和灭活 Erbb 受体的荧光适体
  • 批准号:
    8887479
  • 财政年份:
    2015
  • 资助金额:
    $ 28.44万
  • 项目类别:

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