Developing Nanomaterial Platform for Intra-Cartilage Delivery of RNA Therapeutics against Joint Diseases
Developing Nanomaterial Platform for Intra-Cartilage Delivery of RNA Therapeutics against Joint Diseases
批准号:
10375219
负责人:
Yupeng Chen
金额:
$16.05万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-05-01 至 2023-04-30
关键词:
3-DimensionalADAMTSAdoptedAfrican AmericanAftercareAnalysis of VarianceAnatomyAnimal ModelAnimalsBindingBiomedical EngineeringCartilageCartilage MatrixChargeCollaborationsComputer ModelsComputer softwareControl GroupsDataDegenerative polyarthritisDevelopmentDimensionsDiseaseDisease ProgressionDrug Delivery SystemsEffectivenessFemaleFoundationsFundingFutureGaitGene ExpressionGoalsHumanIndividualInterventionKneeKnee OsteoarthritisKnee jointKnowledgeLearningLeftLengthLimb structureMeasuresMedial meniscus structureMentorsModelingMotionMusMuscleMusculoskeletalNamesNano deliveryOperative Surgical ProceduresOutcomePathologicPopulationProtocols documentationRNA deliveryRehabilitation therapyResearchScienceSmall Interfering RNASurface PropertiesTechniquesTherapeuticTissuesTranslational ResearchTraumaTreatment outcomeUnderrepresented MinorityUnited States National Institutes of HealthWalkingWorkanalytical toolarthropathiesbasecartilage degradationcomputerized toolsdata modelingdesigneffectiveness evaluationexperiencegait examinationimprovedinnovationjoint loadingkinematicsmuscle strengthnanomaterialsneuromuscularnovel therapeuticsovertreatmentparent grantprogramsresponsesimulationspatiotemporaltherapeutic RNAtherapeutic effectivenesstreatment durationtreatment grouptreatment response
中文摘要
项目摘要
拟议的工作支持Yupeng Chen博士的NIH资助的R 01 AR 07207,具有创新的分析和
计算工具来证明他的新技术对促进创伤后疾病的有效性,
骨关节炎(PTOA)的治疗通过抑制软骨退化。陈博士的工作是针对
开发一种非共价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
为了有效减轻软骨变性,将带负电荷的治疗性siRNA引入到
带负电荷的软骨基质没有从软骨基质中清除是两个显著的
挑战因此,陈博士设计了一种方法,通过以下方式克服这些挑战:1)确定
纳米颗粒穿透软骨的最佳尺寸,2)制定纳米颗粒的表面性质,
软骨基质用于组织保留,和3)评价NP抑制PTOA的治疗能力
内侧半月板不稳定(DMM)模型的进展。拟议的支持性分析将有助于
利用步态分析和计算建模来评估通过NP递送的治疗性siRNA如何改变
膝关节负荷因此,设计以下目的以评估治疗性siRNA的有效性
通过NP输送,减少膝关节负荷。
目标1:开发经过验证的三维鼠标模拟
目的2:评估用/不用NP递送的siRNA处理的小鼠中的步态变化
目的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展示NP交付的有效性来支持父母补助金
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,
我和陈博士之间的合作与NIH促进
在科学领域代表性不足的少数群体。总之,这种协作工作有可能改变我们如何
治疗和评估PTOA,如果没有这个鼓励伙伴关系的机会,
来自不同背景的人之间。
英文摘要
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.
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会议论文
Layer-by-Layer Nano Matrix for Growth Plate Regeneration
-
批准号:10373554
-
项目类别:
-
资助金额:$17.85万
-
财政年份:2022
-
负责人:Yupeng Chen
-
依托单位:
Layer-by-Layer Nano Matrix for Growth Plate Regeneration
-
批准号:10649409
-
项目类别:
-
资助金额:$21.43万
-
财政年份:2022
-
负责人:Yupeng Chen
-
依托单位:
Developing Nanomaterial Platform for Intra-Cartilage Delivery of RNA Therapeutics against Joint Diseases
-
批准号:10152524
-
项目类别:
-
资助金额:$34.36万
-
财政年份:2019
-
负责人:Yupeng Chen
-
依托单位:
Developing Nanomaterial Platform for Intra-Cartilage Delivery of RNA Therapeutics against Joint Diseases
-
批准号:10379302
-
项目类别:
-
资助金额:$35.07万
-
财政年份:2019
-
负责人:Yupeng Chen
-
依托单位:
Developing Nanomaterial Platform for Intra-Cartilage Delivery of RNA Therapeutics against Joint Diseases
-
批准号:9367787
-
项目类别:
-
资助金额:$35.42万
-
财政年份:2017
-
负责人:Yupeng Chen
-
依托单位:
Growth Plate Cartilage Repair via Novel Matrilin3/Rosette Nanotube Hybrid Matrix
-
批准号:9338126
-
项目类别:
-
资助金额:$8.05万
-
财政年份:2016
-
负责人:Yupeng Chen
-
依托单位:
Growth Plate Cartilage Repair via Novel Matrilin3/Rosette Nanotube Hybrid Matrix
-
批准号:9038551
-
项目类别:
-
资助金额:$8.05万
-
财政年份:2016
-
负责人:Yupeng Chen
-
依托单位:
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