| 项目编号: | 1510895
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| 项目名称: | UNS: Biomolecular Engineering of siRNAs |
| 作者: | Stephen Walton
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| 承担单位: | Michigan State University
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| 批准年: | 2014
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| 开始日期: | 2015-07-01
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| 结束日期: | 2018-06-30
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| 资助金额: | USD369000
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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
; biochemical engineering program
; rnai pathway protein
; biomolecular therapeutics
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| 英文摘要: | 1510895
Walton, Stephen P.
RNA interference (RNAi) is a natural cellular pathway that can be used to reduce the expression of a targeted protein. This pathway can be activated by double-stranded RNAs called short, interfering RNAs (siRNAs). The specific aims of the proposed work are to: i) define the sequence and structural features of siRNAs that result in the proper processing of siRNAs by the RNAi pathway proteins; ii) characterize the siRNA features that affect binding of the siRNAs by RNAi pathway proteins; and iii) determine the cellular uptake pathways for siRNA-containing complexes that maximize function of the delivered siRNAs. Due to the potential specificity of RNAi and its applicability against nearly any protein target, siRNAs have garnered considerable attention as the next generation of biomolecular therapeutics.
RNA interference holds promise as a tool for manipulation of biological processes and for the development of a new class of therapeutics. RNAi is initiated by short, interfering RNAs (siRNAs) and results in the knockdown of a targeted protein. To achieve knockdown, exogenous siRNAs must be delivered to the cytoplasms of targeted cells and interact productively with the RNAi pathway proteins. However, siRNA delivery remains a significant challenge. To achieve silencing, siRNAs must first enter the targeted cells by a mechanism that allows them to be active. Currently, the uptake pathways that result in siRNA function are poorly understood. The proposed work seeks to identify the rules that govern the design of siRNAs and the vehicles used to deliver them to cells. Using in vitro and cellular systems, siRNAs and delivery vehicles with unique characteristics will be studied to determine which combination of features results in the highest siRNA activity. The specific aims of the proposed work are to i) define the sequence and structural features of siRNAs that are associated with functional asymmetry using an in vitro system; ii) characterize the sequence features that influence in vitro binding interactions of siRNAs with RNAi pathway proteins using degenerate siRNAs and parallel RNA sequencing; and iii) determine the cellular uptake pathways for siRNA-containing complexes that maximize silencing efficiency of the delivered siRNAs.
This award by the Biotechnology and Biochemical Engineering Program of the CBET Division is co-funded by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biology. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/94265
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| Appears in Collections: | 影响、适应和脆弱性
气候减缓与适应
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| Recommended Citation: | |
Stephen Walton. UNS: Biomolecular Engineering of siRNAs. 2014-01-01.
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