EAGER: Collaborative Research: Algorithmic design principles for programmed DNA nanocages

EAGER：协作研究：编程 DNA 纳米笼的算法设计原理

• 批准号: 1547999
• 负责人: Mark Bathe
• 金额: $ 15.5万
• 依托单位: Massachusetts Institute of Technology
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1547999&HistoricalAwards=false
• 关键词: EAGER; Collaborative; Research; Algorithmic; design

3D printing has revolutionized the ability to fabricate complex solid objects at the macroscopic scale using simple Computer-Aided Design (CAD) files as input. In this process, the user specifies the solid object using simple geometric primitives or surface-based meshes. Recent applications of this revolutionary technology include printing limb prosthetics and implants and tissue engineering scaffolds, as well as rapid prototyping of products in industries ranging from apparel and eyeware to automotive, aerospace, and art. A similar transformation in automated fabrication began in the 1970s using CAD for the design of complex electronics using very large scale integration (VLSI) to design circuits consisting of thousands of transistors. This CAD revolution also dramatically increased and broadened the participation of designers without detailed technical know-how needed to design and synthesize custom electrical circuits for diverse applications in industries ranging from mobile devices to biomedical implants. At the nanometer-scale, programmed self-assembly of synthetic DNA offers a similar ability to "print" complex 3D nanometer-scale objects with precisely defined 3D structural features. While the field of structural DNA nanotechnology is considerably younger than the preceding examples, recent technological and scientific advances have enabled the low-cost and reproducible synthesis of diverse structured DNA nano-objects, enabling numerous technological innovations including casting metallic nanoparticles for photonics and light-harvesting devices, fabricating therapeutic vectors that mimic viruses for drug and gene delivery, and developing nanoscale sensors for biomarker detection in disease diagnosis. Structural DNA nanotechnology currently faces a similar bottleneck in the broad participation of designers due to the need for automated CAD-based design software for these nano-objects. Here, development of a next-generation CAD framework is proposed to enable the fully automated design of structured DNA assemblies at the nanometer scale. As a starting point, the development of a CAD program is proposed here for the synthesis of a unique class of DNA-based objects called DNA nanocages. DNA nanocages can be programmed to adopt nearly arbitrary symmetries and sizes on this scale. Further, these DNA-based particles may be functionalized chemically with proteins, RNAs, chromophores, and other small molecules for diverse applications in biomolecular science and technology. In addition, these nanoscale materials can be transformed into structured inorganic materials including metals and silicon dioxide. To realize the aim of transforming the ability to design and fabricate DNA-based nanomaterials, an open-source software package will be developed to prescribe geometrically from the top-down nanocage size and symmetry using a simple high-level language and CAD environment that is distributed worldwide through the world-wide web. Synthetic DNA sequences that self-assemble to form these CAD-specified structures will be automatically generated for nanocage fabrication. Validation of nanocage synthesis will be performed experimentally using high-resolution structural and folding assays. This work forms the starting point for a new high-level programming language to print 3D objects at the nanometer-scale using synthetic DNA that will broadly enable the use and application of these assemblies across diverse research and industrial applications. Future work may extend this framework to arbitrary 2D and 3D DNA-based assemblies, as well as molecularly functionalized DNA-assemblies that mimic, as well as extend far beyond, nature's evolutionary designs.

3D打印已彻底改变了使用简单的计算机辅助设计（CAD）文件作为输入来制造复杂的固体对象的能力。在此过程中，用户使用简单的几何原语或基于表面的网格指定实体对象。这项革命性技术的最新应用包括打印肢体假肢和植入物以及组织工程脚手架，以及从服装和眼神到汽车，航空航天和艺术的行业中产品的快速原型制作。 1970年代，使用CAD开始使用非常大的集成（VLSI）来设计由数千个晶体管组成的电路，从而在1970年代使用CAD进行了类似的转换。这场CAD革命还大大增加了设计师的参与并扩大了设计师的参与，而无需详细的技术知识，以设计和合成从移动设备到生物医学植入物的行业中的各种应用程序的定制电路。在纳米尺度上，合成DNA的编程自组装具有类似的“打印”复杂3D纳米尺度对象具有精确定义的3D结构特征的能力。尽管结构性DNA纳米技术的领域比上一个示例要年轻得多，但最新的技术和科学进步使得能够对多种结构化DNA纳米对象的低成本和可重复的合成，从而实现了许多技术创新，包括用于光子和光子纳米学的铸造金属纳米颗粒，收集设备，制造模拟药物和基因输送病毒的治疗载体，以及开发纳米级传感器以在疾病诊断中进行生物标志物检测。由于需要针对这些纳米对象的自动化基于CAD的设计软件，因此结构性DNA纳米技术目前在设计人员的广泛参与中也面临着类似的瓶颈。在这里，提出了下一代CAD框架的开发，以在纳米尺度上实现结构化DNA组件的全自动设计。作为起点，这里提出了一个CAD程序的开发，以合成一类称为DNA纳米元的独特基于DNA的对象。可以对DNA纳米量表进行编程，以在此规模上采用几乎任意的对称性和大小。此外，这些基于DNA的颗粒可以用蛋白质，RNA，发色团和其他小分子在生物分子科学和技术中进行化学化。此外，这些纳米级材料可以转化为结构化的无机材料，包括金属和二氧化硅。为了实现改变设计和制造基于DNA的纳米材料的能力的目的，将开发一个开源软件包，以使用简单的高级语言和CAD环境从自上而下的纳米层尺寸和对称性中进行几何规定。通过全球网络在全球范围内分发。自组成这些CAD指定结构的合成DNA序列将自动生成纳米型制造。将使用高分辨率的结构和折叠测定法实验进行纳米合成的验证。这项工作构成了一种新的高级编程语言的起点，可以使用合成DNA在纳米尺度上打印3D对象，该对象将在各种研究和工业应用中广泛地使用和应用这些组件。未来的工作可能将此框架扩展到任意的2D和3D基于DNA的组件，以及模拟的分子功能化的DNA组装，并且远远超出了自然的进化设计。