F31 Fellowship Award Childcare Supplement

项目总结 核酸纳米颗粒(NANP)具有同时传递多个 治疗性核酸(TNA)可以通过靶向几种生物途径来治疗疾病。但是，在 为了发挥作用，NNP需要一辆运输工具进入牢房，同时受到自然保护 发生的核酸酶。 已有研究表明，端胺聚酰胺胺(-NH2)PAMAM树枝状大分子 已经成功地将TNA，如小干扰RNA和微小RNA有效地输送到细胞中 保护它们，但这些研究只深入到一代树枝状大分子。这项建议旨在 研究和比较五代不同的(-NH2)PAMAM树枝状大分子，以解释每一代将如何 充当几个有代表性的NANP的载体。 第二个将被调查的递送平台是从癌症和癌症中获得的外体 非癌性人类细胞系。外体自然地将生物信息从一个细胞传递到另一个细胞 正在利用这种自然的通信机制来提供NANP。每个exosome携带不同的生物标志物 与起源的细胞系相对应，这些生物标志物可以用来识别外切体类型和调谐 它们的生物分布、免疫识别和细胞摄取。与外体鉴定一起， 嵌入到外切体复合体中的NANP可能还有助于它们的生物学行为，这是 我们希望在当前的提案中调查什么。 一旦参赛，这项调查将提供关于人工和自然角色的信息 发生的车辆对免疫反应和疗效以及NANP的结构参数如何 (例如，3D VS 2D VS 1D)影响它们的递送和免疫反应。的广泛和长期目标 这项工作将对一个专注于NANP的体外行为的数据库进行分类，这些NANP与其复杂的 载体包括NANP载体平台的免疫反应、保护和功效。在收集这本书时 数据，并对其进行汇编，未来的核酸疗法可以合理地设计出特定的 参数和量身定制的免疫识别和功能，基于患者的需要。 所有建议的实验将由申请者完成，申请者将与必要的 个人需要学习任何必要的补充技术。除了完成拟议的工作外， 申请者将在一个以上的研究生组织担任领导，在这些组织中申请者将获得 在会议上展示这项工作时所需的专业、沟通和领导能力。 北卡罗来纳大学夏洛特分校是一个正在经历指数级增长的空间， 并为学生和研究人员提供了宝贵的资源以供利用。

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.