Investigating and Characterizing Non-Viral, Biocompatible Delivery Vehicles for Nucleic Acid Nanoparticles

研究和表征核酸纳米粒子的非病毒、生物相容性递送载体

基本信息

  • 批准号:
    10629227
  • 负责人:
  • 金额:
    $ 3.93万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-05-16 至 2024-05-15
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY Nucleic acid nanoparticles (NANPs) have the ability to simultaneously deliver a cocktail of multiple therapeutic nucleic acids (TNAs) that can treat diseases by targeting several biological pathways. However, in order to be functional, NANPs require a delivery vehicle to enter cells while being protected from naturally occurring nucleases. There have been studies showing that amine-terminated polyamidoamine (-NH2) PAMAM dendrimers have successfully delivered TNAs such as small interfering RNAs, and micro RNAs into cells while efficiently protecting them, but these studies deep dive into only one generation of dendrimers. This proposal aims to investigate and compare five different generations of (-NH2) PAMAM dendrimers to interpret how each will behave as a carrier for several representative NANPs. A second delivery platform that will be investigated are exosomes that are harvested from cancerous and non-cancerous human cell lines. Exosomes naturally pass biological information from cell to cell and we would be utilizing this natural communication machinery to deliver NANPs. Each exosome carries different biomarkers corresponding to the cell line of origin, and these biomarkers can be used to identify the exosome type and tune their biodistribution, immunorecognition and cellular uptake. Along with exosomal identification, the type of the NANP embedded into the exosome complex may additionally contribute to their biological behavior, which is what we would like to investigate in this current proposal. Once competed, this investigation will supply information regarding the role that synthetic and naturally occurring vehicles have on immune response and efficacy, as well as how NANPs' architectural parameters (e.g., 3D vs 2D vs 1D) influence their delivery and immune response. The broad and long-term objectives for this work would be to categorize a database focused on the in vitro behavior of NANPs complexed to their vehicles to include the immune response, protection, and efficacy of the NANP-carrier platform. In collecting this data, and compiling it, future nucleic acid based therapeutics could be rationally designed with specific parameters and tailored immune recognition and function based on what a patient requires. All proposed experiments will be completed by the applicant who will collaborate with the necessary personal to learn any supplemental techniques needed. In addition to completing the proposed work, the applicant will be serving as a leader in more than one graduate organization where the applicant will be gaining professional, communicative, and leadership skills needed to network when presenting this work at conferences. The University of North Carolina at Charlotte is a space that is experiencing exponential growth that is focused on student success and provides valuable resources for students and researchers to utilize.
项目摘要 核酸纳米颗粒(NANP)具有同时递送多种核酸的混合物的能力。 治疗性核酸(TNAs)可以通过靶向几种生物途径来治疗疾病。但在 为了发挥功能,NANP需要一种递送载体进入细胞,同时受到自然保护, 发生的核酸酶。 已经有研究表明,胺封端的聚酰胺-胺(-NH 2)PAMAM树枝状聚合物 已经成功地将TNA如小干扰RNA和微小RNA递送到细胞中,同时有效地 保护它们,但这些研究只深入研究了一代树枝状聚合物。这项建议旨在 研究和比较五代不同的(-NH 2)PAMAM树枝状聚合物,以解释每一代将如何 作为几种代表性NANP的载体。 将被研究的第二种递送平台是从癌性和非癌性组织中收获的外泌体。 非癌人类细胞系。外泌体自然地将生物信息从细胞传递到细胞, 利用这种自然的沟通机制来提供NANP。每个外泌体携带不同的生物标志物 对应于起源细胞系,这些生物标志物可用于识别外泌体类型和调节 它们的生物分布、免疫识别和细胞摄取。沿着外泌体鉴定, 嵌入外泌体复合物中的NANP可能另外有助于它们的生物学行为, 我们希望在目前的提案中调查什么。 一旦完成,这项调查将提供有关合成和天然作用的信息, 发生的车辆对免疫反应和功效,以及如何NANP的结构参数 (e.g., 3D vs 2D vs 1D)影响它们的递送和免疫反应。广泛和长期的目标, 这项工作将是对一个数据库进行分类,该数据库集中于与其复合的NANP的体外行为。 载体以包括NANP-载体平台的免疫应答、保护和功效。在收集这些 数据,并编译它,未来的基于核酸的治疗可以合理地设计与特定的 参数和定制的免疫识别和功能的基础上,什么病人的需要。 所有拟议的实验将由申请人完成,申请人将与必要的 个人学习所需的任何补充技术。除了完成拟议的工作外, 申请人将在一个以上的研究生组织中担任领导者,申请人将获得 在会议上展示这项工作时,需要具备专业、沟通和领导能力。 位于夏洛特的北卡罗来纳州大学是一个正在经历指数级增长的空间, 对学生的成功,并提供了宝贵的资源,为学生和研究人员利用。

项目成果

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Yelixza Avila其他文献

Yelixza Avila的其他文献

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{{ truncateString('Yelixza Avila', 18)}}的其他基金

F31 Fellowship Award Childcare Supplement
F31 奖学金奖儿童保育补助金
  • 批准号:
    10631008
  • 财政年份:
    2022
  • 资助金额:
    $ 3.93万
  • 项目类别:

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