| 项目编号: | 1653702
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| 项目名称: | CAREER: Assembly of Nanopieces for Controlled Penetration and Binding of Difficult-to-Reach Cartilage Matrix for siRNA Therapy against Osteoarthritis |
| 作者: | Yupeng Chen
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| 承担单位: | Rhode Island Hospital
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| 批准年: | 2017
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| 开始日期: | 2017-06-01
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| 结束日期: | 2022-05-31
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| 资助金额: | 503125
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| 资助来源: | US-NSF
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| 项目类别: | Standard Grant
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| 国家: | US
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| 语种: | 英语
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| 特色学科分类: | Engineering - Chemical, Bioengineering, Environmental, and Transport Systems
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| 英文关键词: | sirna
; self-assembly
; oa
; proposal
; negatively-charged sirnas
; first sirna therapy
; barrington high school
; negatively-charged tissue matrix
; joint cartilage
; delicate self-assembly process
; assembly process
; binding ability
; rnt/sirna architecture
; career development plan
; matrix metalloproteinase-13
; tissue matrix
; sirna delivery vehicle
; matrix-rich tissue
; outreach plan
; therapeutic sirna
; tissue matrix molecule
; sirna approach
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| 英文摘要: | PI: Chen, Yupeng
Proposal #: 1653702
Osteoarthritis (OA) affects approximately 13.9% of Americans aged 25 years and older. This equates to an estimated 30 million people in the United States, making it one of the leading causes of disability. OA is a degenerative joint disease involving in the degeneration of joint cartilage. This leads to pain, stiffness, movement problems, and activity limitations. Currently, there is no clinically successful therapeutic to against OA. As a Nobel-prize winning discovery, siRNA can effectively and specifically inhibit disease gene expression, which provides a great therapeutic potential to treat OA. However, it is extremely challenging to deliver negatively-charged siRNAs to infiltrate avascular, dense, negatively-charged tissue matrix, such as cartilage. This research will develop a novel delivery vehicle, which can self-assemble with therapeutic siRNAs and deliver them into matrix-rich tissues in an effective and safe manner.
The proposed study will focus on understanding the delicate self-assembly process between rosette nanotubes (RNTs) and siRNA into non-covalent architectures. By mediating the assembly process, the RNT/siRNA architectures will be constructed into siRNA delivery vehicles of various sizes and shapes. Then, their ability to penetrate tissue matrix and deliver siRNA will be analyzed and optimized. This proposal will also identify and manipulate the binding ability of these non-covalent delivery vehicles with tissue matrix molecules to achieve effective and long-lasting inhibition of matrix metalloproteinase-13 (MMP-13), a key disease gene during OA progression. Furthermore, the therapeutic potential of this siRNA approach against OA will be evaluated in an animal model. In addition, this proposal provides a plan to merge the gap between science and medical education and train the next generation of scientists and clinicians with interdisciplinary knowledge and encourage them to translate science, engineering and technology innovations to satisfy clinical needs. Lastly, collaborating with the Barrington High School (BHS) in Rhode Island, this proposal will develop an outreach plan to introduce nanotechnology to high school students and demonstrate to them how it can help overcome "real-life problems" in clinics. Beyond achieving the specific goals of this proposal, this career development plan can significantly improve scientific understanding of the self-assembly of non-covalent structures as well as lay the foundation for the development of the first siRNA therapy to inhibit OA progression. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/90050
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| Appears in Collections: | 全球变化的国际研究计划
科学计划与规划
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| Recommended Citation: | |
Yupeng Chen. CAREER: Assembly of Nanopieces for Controlled Penetration and Binding of Difficult-to-Reach Cartilage Matrix for siRNA Therapy against Osteoarthritis. 2017-01-01.
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