CAREER: Nucleic acid circuitry for programming gene expression

职业：用于编程基因表达的核酸电路

• 批准号: 0954566
• 负责人: Georg Seelig
• 金额: $ 40万
• 依托单位: University of Washington
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-15 至 2016-01-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0954566&HistoricalAwards=false
• 关键词: CAREER; Nucleic; acid; circuitry; programming

0954566SeeligThe proposed work will enable a potentially transformative technology for controlling cellular behavior using nucleic acids. The PI will engineer synthetic molecular circuitry that can analyze RNA expression inside living cells and { based on this analysis { autonomously control gene expression. The PI will show that nucleic acid circuitry can distinguish between di_erent cell types and states and can specifically regulate a target gene only in a subset of cells. A central aim of this project is to increase the specificity of conventional antisense and siRNA-based therapeutics by combining drug delivery with sensing and logic. Specific research objectives are: (i) The design of hybridization-based molecular sensors for the detection of RNA in living cells; (ii) the design of controllable molecular actuators based on antisense oligonucleotides and silencing RNA; (iii) the construction of integrated sensor-actuator systems for conditional gene regulation. This program provides the basis for the construction of complex multi-component circuits for programmable control of gene expression. This work will lead to new molecular tools for temporal and spatial control of gene expression, with the potential for wide-spread applications in disease therapy and in basic biology research. The proposed research is tightly integrated with an outreach program with two main aims. The first aim is to develop an educational framework that teaches the interdisciplinary skills required to succeed in synthetic biology research. The second aim is to leverage this framework to attract and engage students who are not traditionally involved with life-science research, or would not consider enrolling in one of the traditional tracks in an electrical engineering or computer science program (the PI's home departments are EE and CS).

0954566Seelig 拟议的工作将实现一种潜在的革命性技术，用于使用核酸控制细胞行为。 PI 将设计合成分子电路，分析活细胞内的 RNA 表达，并{基于此分析{自主控制基因表达。 PI 将表明核酸电路可以区分不同的细胞类型和状态，并且可以仅在细胞子集中特异性调节靶基因。该项目的中心目标是通过将药物输送与传感和逻辑相结合来提高传统反义和基于 siRNA 的疗法的特异性。具体研究目标是： (i) 设计用于检测活细胞中 RNA 的基于杂交的分子传感器； (ii) 基于反义寡核苷酸和沉默RNA的可控分子执行器的设计； (iii) 构建用于条件基因调控的集成传感器-执行器系统。 该程序为构建用于可编程控制基因表达的复杂多组件电路提供了基础。这项工作将带来用于基因表达的时间和空间控制的新分子工具，并具有在疾病治疗和基础生物学研究中广泛应用的潜力。 拟议的研究与具有两个主要目标的外展计划紧密结合。第一个目标是开发一个教育框架，教授合成生物学研究成功所需的跨学科技能。第二个目标是利用这个框架来吸引和吸引那些传统上不参与生命科学研究的学生，或者不会考虑参加电气工程或计算机科学项目的传统课程之一的学生（PI 的所属部门是 EE）和CS）。