Developing Nanomaterial Platform for Intra-Cartilage Delivery of RNA Therapeutics against Joint Diseases

开发用于软骨内递送 RNA 治疗关节疾病的纳米材料平台

基本信息

批准号：
10375219
负责人：
Yupeng Chen
金额：
$ 16.05万
依托单位：
UNIVERSITY OF CONNECTICUT STORRS
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-05-01 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10375219
关键词：
3-Dimensional ADAMTS Adopted African American Aftercare Analysis of Variance Anatomy Animal Model Animals Binding Biomedical Engineering Cartilage Cartilage Matrix Charge Collaborations Computer Models Computer software Control Groups Data Degenerative polyarthritis Development Dimensions Disease Disease Progression Drug Delivery Systems Effectiveness Female Foundations Funding Future Gait Gene Expression Goals Human Individual Intervention Knee Knee Osteoarthritis Knee joint Knowledge Learning Left Length Limb structure Measures Medial meniscus structure Mentors Modeling Motion Mus Muscle Musculoskeletal Names Nano delivery Operative Surgical Procedures Outcome Pathologic Population Protocols documentation RNA delivery Rehabilitation therapy Research Science Small Interfering RNA Surface Properties Techniques Therapeutic Tissues Translational Research Trauma Treatment outcome Underrepresented Minority United States National Institutes of Health Walking Work analytical tool arthropathies base cartilage degradation computerized tools data modeling design effectiveness evaluation experience gait examination improved innovation joint loading kinematics muscle strength nanomaterials neuromuscular novel therapeutics overtreatment parent grant programs response simulation spatiotemporal therapeutic RNA therapeutic effectiveness treatment duration treatment group treatment response

项目摘要

Project Abstract The proposed work supports Dr. Yupeng Chen's NIH-funded R01AR07207 with innovative analytical and computational tools to demonstrate the effectiveness of his new technique for advancing post traumatic osteoarthritis (PTOA) treatment by inhibiting cartilage degeneration. Dr. Chen's work is aimed at the development of a non-covalent Janus-base non-delivery vehicle, Nanopiece (NP), to stop cartilage degeneration by introducing therapeutic small interfering RNA (siRNA) into the cartilage matrix. While siRNA has been shown to be effective in mitigating cartilage degeneration, introducing the negatively charged therapeutic siRNA into the negatively charged cartilage matrix without getting cleared from the cartilage matrix are two significant challenges. Therefore, Dr. Chen has devised an approach that will overcome these challenges by 1) determining the optimal dimensions of NPs to penetrate the cartilage, 2) formulating surface properties of NPs that bind cartilage matrix for tissue retention, and 3) evaluating the therapeutic ability of the NPs to inhibit PTOA progression in the destabilization of medial meniscus (DMM) model. The proposed supporting analyses will serve to utilize gait analysis and computational modeling to evaluate how the therapeutic siRNA delivered via NP alters knee loading. Therefore, the following aims are designed to evaluate the effectiveness of the therapeutic siRNA delivered via NP on reducing knee loading. Aim 1: Develop Validated Three-Dimensional Mouse Simulations Aim 2: Evaluate Gait Changes in Mice With/Without NP Delivered siRNA Treatment Aim 3: Identify Correlations Between Animal and Human Gait Models to Assess Treatment Outcomes The results of this work will support the parent grant by demonstrating the effectiveness of the NP delivered siRNA treatment in inhibiting PTOA progression. Furthermore, through this work I will be mentored by Dr. Chen to learn how to conduct translational research. As an African American female biomedical engineer, this collaboration between myself and Dr. Chen aligns with the NIH efforts to promote the advancement of underrepresented minorities in science. Together, this collaborative work has the potential to transform how we treat and evaluate PTOA and it would not be possible without this opportunity that encourages partnerships between individuals from diverse backgrounds.

项目摘要拟议的工作通过创新的分析和方法支持陈玉鹏博士的 NIH 资助的 R01AR07207 计算工具来证明他的新技术对于推进创伤后治疗的有效性通过抑制软骨退化来治疗骨关节炎（PTOA）。陈博士的工作旨在开发非共价 Janus 基非递送载体 Nanopiece (NP)，以阻止软骨退化通过将治疗性小干扰 RNA (siRNA) 引入软骨基质。虽然 siRNA 已被证明为了有效减轻软骨退化，将带负电荷的治疗性 siRNA 引入带负电的软骨基质没有从软骨基质中清除是两个重要的挑战。因此，陈博士设计了一种方法来克服这些挑战：1）确定纳米粒子穿透软骨的最佳尺寸，2) 制定结合的纳米粒子的表面特性用于组织保留的软骨基质，以及 3) 评估 NP 抑制 PTOA 的治疗能力内侧半月板（DMM）模型不稳定的进展。拟议的支持分析将有助于利用步态分析和计算模型来评估通过 NP 传递的治疗性 siRNA 如何改变膝盖负荷。因此，设计以下目标来评估治疗性siRNA的有效性通过 NP 传递以减少膝盖负荷。目标 1：开发经过验证的三维鼠标模拟目标 2：评估接受/不接受 NP 递送 siRNA 治疗的小鼠的步态变化目标 3：确定动物和人类步态模型之间的相关性以评估治疗结果这项工作的结果将通过证明所提供的 NP 的有效性来支持家长资助 siRNA 治疗抑制 PTOA 进展。此外，通过这项工作，我将得到陈博士的指导学习如何进行转化研究。作为一名非裔美国女性生物医学工程师，这我和陈博士之间的合作与 NIH 的努力相一致，以促进进步科学领域代表性不足的少数群体。总之，这项协作工作有可能改变我们的方式对待和评估 PTOA，如果没有这个鼓励伙伴关系的机会，这是不可能的来自不同背景的个人之间。