Abstract: Described herein is a 3D nanoscale building platform. The platform is based on cube-shaped DNA nanostructures that are rigid enough to preserve cubic shape. Different cubes are connected together through complementary overhangs. We have developed a computational design algorithm that finds the smallest number of different cube types required to self-assemble target 3D shape. Each cube can be functionalized by attaching a cargo inside of it or adjacent to it (e.g., gold nanoparticles, carbon nanotubes, proteins, etc.) and can thus be used as a “scaffold” to construct arbitrary shapes in 3D from individual nanoscale building blocks. The final assembly can be a 3D periodic lattice, or a finite-sized object. From our simulation-designed cubes, we export to an experimental blueprint, where the strands and interactions between them are designed to self-assemble into a target shape.