Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; email:
Annu Rev Biophys. 2019 May 6;48:395-419. doi: 10.1146/annurev-biophys-052118-115259.
Structural DNA nanotechnology is beginning to emerge as a widely accessible research tool to mechanistically study diverse biophysical processes. Enabled by scaffolded DNA origami in which a long single strand of DNA is weaved throughout an entire target nucleic acid assembly to ensure its proper folding, assemblies of nearly any geometric shape can now be programmed in a fully automatic manner to interface with biology on the 1-100-nm scale. Here, we review the major design and synthesis principles that have enabled the fabrication of a specific subclass of scaffolded DNA origami objects called wireframe assemblies. These objects offer unprecedented control over the nanoscale organization of biomolecules, including biomolecular copy numbers, presentation on convex or concave geometries, and internal versus external functionalization, in addition to stability in physiological buffer. To highlight the power and versatility of this synthetic structural biology approach to probing molecular and cellular biophysics, we feature its application to three leading areas of investigation: light harvesting and nanoscale energy transport, RNA structural biology, and immune receptor signaling, with an outlook toward unique mechanistic insight that may be gained in these areas in the coming decade.
结构 DNA 纳米技术开始成为一种广泛应用的研究工具，用于在机械上研究各种生物物理过程。在支架 DNA 折纸的支持下，长单链 DNA 贯穿整个目标核酸组装体以确保其正确折叠，现在几乎可以以全自动的方式编程来与 1-100nm 范围内的生物学相互作用。在这里，我们回顾了主要的设计和合成原则，这些原则使得能够制造一类特定的支架 DNA 折纸物体，称为线框组装体。这些物体提供了对生物分子纳米级组织的前所未有的控制，包括生物分子的拷贝数、在凸面或凹面几何形状上的呈现以及内部与外部的功能化，以及在生理缓冲液中的稳定性。为了突出这种用于探测分子和细胞生物物理学的合成结构生物学方法的强大功能和多功能性，我们以三个主要研究领域的应用为特色：光收集和纳米级能量传输、RNA 结构生物学和免疫受体信号转导，并展望在未来十年可能在这些领域获得独特的机械洞察力。
