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 打印彻底改变了使用简单的计算机辅助设计 (CAD) 文件作为输入在宏观尺度上制造复杂实体物体的能力。在此过程中，用户使用简单的几何图元或基于表面的网格来指定实体对象。这项革命性技术的最新应用包括打印肢体假肢、植入物和组织工程支架，以及从服装和眼镜到汽车、航空航天和艺术等行业的产品快速原型制作。自动化制造领域的类似转变始于 20 世纪 70 年代，使用 CAD 来设计复杂的电子产品，使用超大规模集成 (VLSI) 来设计由数千个晶体管组成的电路。这场 CAD 革命还极大地增加和扩大了设计人员的参与度，而无需详细的技术知识即可为从移动设备到生物医学植入物等行业的各种应用设计和合成定制电路。在纳米尺度上，合成 DNA 的编程自组装提供了类似的能力，可以“打印”具有精确定义的 3D 结构特征的复杂 3D 纳米尺度物体。虽然结构 DNA 纳米技术领域比前面的例子要年轻得多，但最近的技术和科学进步已经实现了多种结构 DNA 纳米物体的低成本和可重复合成，从而实现了众多技术创新，包括为光子学和光捕获设备铸造金属纳米颗粒、制造模仿病毒的药物和基因治疗载体 交付，并开发用于疾病诊断中生物标志物检测的纳米级传感器。由于这些纳米物体需要基于 CAD 的自动化设计软件，结构 DNA 纳米技术目前在设计师的广泛参与方面也面临着类似的瓶颈。这里，建议开发下一代 CAD 框架，以实现纳米级结构化 DNA 组件的全自动设计。作为起点，本文建议开发 CAD 程序，用于合成一类独特的基于 DNA 的物体，称为 DNA 纳米笼。 DNA 纳米笼可以通过编程在这个尺度上采用几乎任意的对称性和尺寸。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进行化学功能化，用于生物分子科学和技术中的各种应用。此外，这些纳米级材料可以转化为包括金属和二氧化硅在内的结构化无机材料。为了实现转变设计和制造基于 DNA 的纳米材料的能力的目标，将开发一个开源软件包，使用简单的高级语言和 CAD 环境（通过万维网在全球范围内分发）从自上而下地规定纳米笼的尺寸和对称性。将自动生成用于纳米笼制造的自组装形成这些 CAD 特定结构的合成 DNA 序列。纳米笼合成的验证将通过高分辨率结构和折叠测定进行实验。这项工作构成了一种新的高级编程语言的起点，该语言可以使用合成 DNA 在纳米级打印 3D 物体，这将使这些组件在不同的研究和工业应用中广泛使用和应用。未来的工作可能会将这个框架扩展到任意基于 2D 和 3D DNA 的组件，以及模仿并远远超出自然进化设计的分子功能化 DNA 组件。