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

项目摘要 拟议的工作为陈玉鹏博士的NIH资助的R01AR07207提供了创新的分析和 证明他的新技术在推进创伤后治疗中的有效性的计算工具 通过抑制软骨退变来治疗骨关节炎(PTOA)。陈博士的工作是针对 阻止软骨退变的非共价Janus基非共价载体纳米微粒的研制 通过将治疗性小干扰RNA(SiRNA)引入软骨基质中。虽然siRNA已经被证明 为了有效缓解软骨退变，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，这有两个重要的意义 挑战。因此，陈博士设计了一种方法，通过确定1)来克服这些挑战 NPs穿透软骨的最佳尺寸，2)形成结合的NPs的表面性质 3)评价纳米粒抑制PTOA的治疗能力。 内侧半月板失稳模型的研究进展。拟议的支持性分析将有助于 利用步态分析和计算模型来评估通过NP传递的治疗性siRNA是如何改变的 膝盖负重。因此，以下目的旨在评估治疗性siRNA的有效性 通过NP提供减少膝部负荷。 目标1：开发经过验证的三维老鼠模拟 目的2：评价NP-siRNA治疗前后小鼠步态的变化 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交付的NP的有效性来支持父母赠款 SiRNA治疗对PTOA进展的抑制作用。此外，通过这项工作，我将得到陈博士的指导 学习如何进行翻译研究。作为一名非裔美国女性生物医学工程师， 我和陈博士之间的合作与NIH促进 在科学界代表不足的少数群体。总而言之，这种协作工作有可能改变我们 治疗和评估PTOA，没有这个鼓励伙伴关系的机会是不可能的 来自不同背景的人之间的关系。

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.