Engineering a DNA-based nanodevice to enable cytosolic transport of enzymes

设计基于 DNA 的纳米装置以实现酶的胞质运输

• 批准号: 1402756
• 负责人: Silvia Muro
• 金额: $ 35万
• 依托单位: University of Maryland, College Park
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-01 至 2017-05-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1402756&HistoricalAwards=false
• 关键词: Engineering; DNA; based; nanodevice; enable

AbstractProposal Number: 1402756 P.I.: Muro, Silvia Institution: University of Maryland College ParkTitle: Engineering a DNA-based nanodevice to enable cytosolic transport of enzymesThis project aims at designing tools to enable safe, specific, and efficient access into the interior of live cells, which is elusive to current technologies. This is achieved by leveraging on the material that cells naturally use to store their genetic information and re-engineering this material into tiny devices capable to interact and be transported into cells. The project encompasses characterization of these devices, evaluation of their interaction with live cells, and investigation of their effects. By providing access into live cells, this technology has a very broad potential: it can be used to study how cells function and also to manipulate their activity, which is important to enable research, to exploit cells as factories and machines, and to design new diagnostic and therapeutic tools. This has relevance to advance fundamental knowledge in a variety of disciplines, such as molecular and cellular biology, biomaterials, bioengineering, nanotechnology, etc., and to impact biotechnological production, biopharmaceutical development, and medical applications. The fundamental concepts, methods, and tools developed are also integrated into educational and training components, which involve high school, undergraduate, and graduate students, hence, contributing to training future scientists, engineers, educators, and other workforce. Products of this project are used for scientific divulgation to the specialized and broader community, as well as interaction with industry, to maximize its fundamental and translational impact at a local, national, and global level.The objective of this project is to design and optimize a DNA-based nanodevice to enable safe, specific, and efficient access of biomolecules to the cell interior, which currently remains elusive. This is achieved by exploiting newly discovered properties of DNA, which arise from engineering this natural polymer into architectures different from those available in nature. Briefly, DNA is engineered to acquire a dendrimeric conformation functionalized to carry biomolecules and to target specific cell-surface markers, which renders precise interaction with selected cells, uptake via precise endocytic pathways, and cytosolic delivery with transport to intracellular sites of choice. The three aims explored include characterization of DNA systems with different biophysical properties, evaluation of their interaction with cells, and investigation of their effects in cells. This enables intracellular access of probes, modulatory agents, diagnostics, therapeutics, etc., which has applications in fundamental research, biotechnological production, biopharmaceutical development, and medical applications. By leveraging on diverse disciplines such as cellular biology, biotechnology, bioengineering, nanotechnology, and biopharmaceuticals, this project also contributes tools, methods, and knowledge pertaining to these areas. This is further integrated into educational and training components, which involve high school, undergraduate, and graduate students,contributing to training the future workforce.This award by the Biotechnology, Biochemical, and Biomass Engineering Program of the CBET Division is co-funded by the Instrument Development for Biological Research Program of the Division of Biological Infrastructure.

摘要提案编号：1402756 P.I: Muro， Silvia机构：University of Maryland College park标题：设计一种基于dna的纳米器件，使酶能够在细胞质内运输本项目旨在设计一种工具，使酶能够安全、特异性和高效地进入活细胞内部，这是目前技术难以实现的。这是通过利用细胞自然用来储存遗传信息的物质，并将这种物质重新设计成能够相互作用并被运送到细胞中的微小设备来实现的。该项目包括表征这些设备，评估其与活细胞的相互作用，并调查其影响。通过提供进入活细胞的途径，这项技术具有非常广泛的潜力：它可以用来研究细胞的功能，也可以用来操纵它们的活动，这对于实现研究，利用细胞作为工厂和机器，以及设计新的诊断和治疗工具非常重要。这与推进各种学科的基础知识相关，如分子和细胞生物学、生物材料、生物工程、纳米技术等，并影响生物技术生产、生物制药开发和医学应用。开发的基本概念、方法和工具也集成到教育和培训组件中，涉及高中、本科生和研究生，因此有助于培训未来的科学家、工程师、教育工作者和其他劳动力。该项目的产品用于向专业和更广泛的社区进行科学传播，以及与工业界的互动，以最大限度地提高其在地方、国家和全球层面的基础和转化影响。该项目的目标是设计和优化一种基于dna的纳米器件，使生物分子能够安全、特异、高效地进入细胞内部，这一点目前仍是难以捉摸的。这是通过利用新发现的DNA特性来实现的，这些特性是通过将这种天然聚合物设计成不同于自然界中可用的结构而产生的。简而言之，DNA被改造成具有功能的树突构象，可以携带生物分子并靶向特定的细胞表面标记物，从而与选定的细胞进行精确的相互作用，通过精确的内吞途径摄取，并将细胞质输送到选定的细胞内位置。探索的三个目标包括具有不同生物物理特性的DNA系统的特征，评估它们与细胞的相互作用，以及研究它们在细胞中的作用。这使得细胞内的探针，调节剂，诊断，治疗等，这在基础研究，生物技术生产，生物制药开发和医疗应用中的应用。通过利用不同的学科，如细胞生物学、生物技术、生物工程、纳米技术和生物制药，该项目还为这些领域提供了工具、方法和知识。这进一步整合到教育和培训部分，涉及高中，本科生和研究生，有助于培养未来的劳动力。该奖项由CBET部门的生物技术、生化和生物质工程项目颁发，由生物基础设施部门的生物研究仪器开发项目共同资助。