F31 Fellowship Award Childcare Supplement

F31 奖学金奖儿童保育补助金

• 批准号: 10631008
• 负责人: Yelixza Avila
• 金额: $ 0.25万
• 依托单位: UNIVERSITY OF NORTH CAROLINA CHARLOTTE
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/10631008
• 关键词: 3-Dimensional; Address; Amines; Architecture; Award; Back; Behavior; Binding; Biodistribution; Biological; Biological Assay; Biological Markers; Cancer cell line; Cancerous; Cations; Cell Line; Cell Survival; Cells; Clinical; Communication; Complex; DNA; Data; Databases; Dendrimers; Dimensions; Disease; Electrostatics; Fellowship; Fiber; Formulation; Future; Gene Silencing; Generations; Genetic; Growth; Harvest; Human; Human Cell Line; Immune; Immune response; Immune system; Immunization; Investigation; Leadership; Learning; MicroRNAs; Modality; Nanotechnology; North Carolina; Nucleic Acids; Pathway interactions; Patients; Pharmacologic Substance; Property; RNA; RNA Interference Therapy; Research; Research Personnel; Resources; Role; Shapes; Small Interfering RNA; Structure; Students; Techniques; Testing; Therapeutic; Therapeutic Agents; Transfection; Universities; Virus Diseases; Western Blotting; Work; analog; base; behavior in vitro; biomaterial compatibility; clinically relevant; comparative; delivery vehicle; design; exosome; experience; experimental study; in vitro Assay; interest; nanocarrier; nanoparticle; nuclease; nucleic acid-based therapeutics; personalized therapeutic; pre-clinical; prevent; programs; rational design; scaffold; skills; success; symposium; uptake

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）具有同时提供多重鸡尾酒的能力 可以通过靶向多种生物学途径来治疗疾病的治疗核酸（TNA）。但是，在 为了发挥功能，NANP需要送货车才能进入牢房，同时受到自然保护 发生的核武器。 有研究表明，胺终止的多酰胺（-NH2）PAMAM树状聚合物 成功地将TNA（例如小干扰RNA）和微RNA传递到细胞中，同时有效 保护它们，但这些研究只会深入研究一代树枝状聚合物。该建议旨在 调查并比较五个不同世代的（-nh2）PAMAM树枝状聚合物以解释如何 作为几个代表Nanps的载体。 将要研究的第二个送货平台是从取消和 非癌性人类细胞系。外泌体自然将生物学信息从细胞传递到细胞，我们将 使用这种自然通信机械提供NANPS。每个外泌体都带有不同的生物标志物 对应于原点细胞系，这些生物标志物可用于识别外泌体类型和调整 它们的生物分布，免疫认知和细胞摄取。与外泌体认同一起， 嵌入外泌体复合物中的NANP可能会促进其生物学行为，这是 我们想在当前的建议中调查。 一旦竞争，这项投资将提供有关合成和自然作用的信息 发生的车辆具有免疫反应和效率，以及Nanps的建筑参数 （例如，3D vs 2d vs 1d）影响其输送和免疫反应。广泛的长期目标 这项工作将是分类的数据库，该数据库侧重于Nanps的体外行为 车辆包括NANP载体平台的免疫响应，保护和效率。收集这个 数据和编译，​​未来基于核酸的疗法可以合理设计 根据患者的要求，参数和量身定制的免疫认知和功能。 所有提出的实验将由申请人完成，他们将与必要的合作 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 在会议上展示这项工作时，需要进行专业，沟通和领导技能。 北卡罗来纳大学夏洛特分校是一个指数增长的空间 关于学生的成功，并为学生和研究人员提供宝贵的资源。