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

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.