Tissue Adhesive RNA Interference Nanoparticles to Block Progression of Posttraumatic and Spontaneous Osteoarthritis.

组织粘附 RNA 干扰纳米颗粒可阻止创伤后和自发性骨关节炎的进展。

基本信息

  • 批准号:
    10539405
  • 负责人:
  • 金额:
    $ 62.21万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-08-22 至 2027-07-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY/ABSTRACT Osteoarthritis (OA) results from a combination of natural wear and tear associated with aging and/or unnatural mechanical loading on the joint. Patients who suffer a joint injury (e.g., ligament damage) have increased risk for early development of OA. Injury-related post-traumatic osteoarthritis (PTOA) often occurs in younger patients. PTOA and OA are both associated with articular cartilage erosion and other joint changes that cause pain and loss in quality of life. The available treatments only provide temporary pain relief. However, alleviation of pain only briefly masks the disease and does not halt or slow its progression. Progression of PTOA/OA to the point where joint replacement becomes necessary is almost inevitable for large joints because there are currently no disease-modifying osteoarthritis drugs (DMOADs) that can stop progression of or cure the disease. Loss of cartilage associated with OA and PTOA is driven by local upregulation of matrix metalloproteinases (MMPs). We propose that blocking the cartilage-degrading MMPs could stop the progression of PTOA/OA, improve quality of life, and reduce the need for joint replacement in afflicted patients. Pharmaceutical companies have previously tested drugs that can block the activity of MMPs, but these treatments have failed, primarily because their lack of specificity and lack of delivery approaches that localize the drug to the affected joint. We propose to develop intra-articularly injected bioadhesive nanoparticles for locally-retained delivery of short interfering RNA (bioad-si-NPs). The bioad-si-NPs will potently and specifically “knock down” specific MMPs to halt cartilage degradation in joints with OA or at risk of OA development (following injury). The mechanism of siRNA enables these molecules to be selective for specific MMPs, and the bioad-si-NPs are designed to be retained locally at the site of intra-articular delivery; both of these features contribute to our approach having reduced risk of off target side effects. We will test bioad-si-NPs in animal models of both PTOA and spontaneous OA and for inhibition of single or combinations of MMPs. In the setting of spontaneous OA, we will also test the value of initiating treatment at early versus more advanced stages of disease. This project is uniquely accessible through the interdisciplinary team with bioengineering expertise in intracellular biologic drug delivery nanotechnologies and RNA chemistry (Duvall), OA biology and animals models (Hasty), analysis of PTOA/OA animal model joint function/pain (Krug), and clinical care of OA patients (Crofford).
项目总结/文摘

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Craig Lewis Duvall其他文献

Craig Lewis Duvall的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Craig Lewis Duvall', 18)}}的其他基金

Next Gen Targeted nanoparticles for Inhibiting Gli2 in Bone Metastatic Tumors
用于抑制骨转移肿瘤中 Gli2 的下一代靶向纳米颗粒
  • 批准号:
    10623705
  • 财政年份:
    2023
  • 资助金额:
    $ 62.21万
  • 项目类别:
Tissue Adhesive RNA Interference Nanoparticles to Block Progression of Posttraumatic and Spontaneous Osteoarthritis.
组织粘附 RNA 干扰纳米颗粒可阻止创伤后和自发性骨关节炎的进展。
  • 批准号:
    10688080
  • 财政年份:
    2022
  • 资助金额:
    $ 62.21万
  • 项目类别:
Albumin hitchhiking siRNAs for gene targeting in aged brain
白蛋白搭便车 siRNA 用于老年大脑基因靶向
  • 批准号:
    10611521
  • 财政年份:
    2022
  • 资助金额:
    $ 62.21万
  • 项目类别:
Albumin hitchhiking siRNAs for gene targeting in aged brain
白蛋白搭便车 siRNA 用于老年大脑基因靶向
  • 批准号:
    10467737
  • 财政年份:
    2022
  • 资助金额:
    $ 62.21万
  • 项目类别:
Albumin Binding siRNAs for Systemic Treatment of Multi-Joint Osteoarthritis
白蛋白结合 siRNA 用于多关节骨关节炎的全身治疗
  • 批准号:
    10358582
  • 财政年份:
    2021
  • 资助金额:
    $ 62.21万
  • 项目类别:
Hybrid Synthetic and Biologic Shear Thinning Hydrogels for Diabetic Wound Healing
用于糖尿病伤口愈合的混合合成和生物剪切稀化水凝胶
  • 批准号:
    10446305
  • 财政年份:
    2021
  • 资助金额:
    $ 62.21万
  • 项目类别:
Hybrid Synthetic and Biologic Shear Thinning Hydrogels for Diabetic Wound Healing
用于糖尿病伤口愈合的混合合成和生物剪切稀化水凝胶
  • 批准号:
    10245000
  • 财政年份:
    2019
  • 资助金额:
    $ 62.21万
  • 项目类别:
Hybrid Synthetic and Biologic Shear Thinning Hydrogels for Diabetic Wound Healing
用于糖尿病伤口愈合的混合合成和生物剪切稀化水凝胶
  • 批准号:
    10668940
  • 财政年份:
    2019
  • 资助金额:
    $ 62.21万
  • 项目类别:
Hybrid Synthetic and Biologic Shear Thinning Hydrogels for Diabetic Wound Healing
用于糖尿病伤口愈合的混合合成和生物剪切稀化水凝胶
  • 批准号:
    10005338
  • 财政年份:
    2019
  • 资助金额:
    $ 62.21万
  • 项目类别:
MK2 Inhibitory Nanoplexes to Enhance Long-Term Vascular Graft Patency
MK2 抑制性纳米复合物可增强血管移植物的长期通畅性
  • 批准号:
    9463239
  • 财政年份:
    2016
  • 资助金额:
    $ 62.21万
  • 项目类别:

相似海外基金

RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 62.21万
  • 项目类别:
    Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 62.21万
  • 项目类别:
    Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 62.21万
  • 项目类别:
    Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 62.21万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 62.21万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 62.21万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 62.21万
  • 项目类别:
    Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
  • 批准号:
    2301846
  • 财政年份:
    2023
  • 资助金额:
    $ 62.21万
  • 项目类别:
    Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 62.21万
  • 项目类别:
    Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
  • 批准号:
    23K16076
  • 财政年份:
    2023
  • 资助金额:
    $ 62.21万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了