Self-assembly of three-dimensional nucleic acid nanostructures

Abstract

Patterning complex 3D features at the nanoscale offers potential applications for a wide range of fields from materials to medicine. While numerous methods have been developed to manipulate nanoscale materials, these methods are typically limited by their difficulty in creating arbitrary 3D patterns. Self-assembly of nucleic acids has emerged as a promising method for addressing this challenge due to the predictability and programmability of the material and its structure. While a diversity of DNA nanostructures have been designed by specifying complementarity rules between strands, creation of 3D nanostructures requires careful design of strand architecture, and patterns are often limited to a volume of 25 x 25 x 25 nm³ Here, we address the challenges in structural DNA nanotechnology by developing a modular DNA "brick" approach. These bricks are short, single-stranded oliogomers that can self-assemble in a single-pot reaction to a prescribed 3D shape. Using this modular approach, we demonstrate high efficiency in 3D design by generating 100 distinct, discrete 3D structures from a library of strands. We also created long-range ordering of channels, tunnels, and pores by growing micron-sized 3D periodic crystals made from DNA bricks. Finally, we applied this approach to control over 30,000 unique component strands to selfassemble into cuboids measuring over 100 nm in each dimension. These structures were further used to pattern highly complex cavities. Together, this work represents a simple, modular, and versatile method for 3D nanofabrication. This unique patterning capability of DNA bricks may enable development of new applications by providing a foundation for intricate and complex control of an unprecedented number of independent components.