The authors describe a novel method for constructing complex three-dimensional (3D) structures using short synthetic DNA strands, referred to as "DNA bricks." Each DNA brick is a 32-nucleotide single-strand with four 8-base binding domains, allowing it to bind to four neighbors and form a modular component. In one-step annealing reactions, these bricks self-assemble into prescribed 3D shapes without the need for a scaffold strand. The modular nature of the method allows for the construction of 102 distinct shapes with intricate features, including solid shapes with sophisticated geometries and surface patterns, as well as hollow shapes with tunnels and cavities. The authors also demonstrate the versatility of the method by constructing structures with alternative packing geometries and using non-canonical brick motifs. This work establishes DNA bricks as a robust and versatile framework for creating complex 3D nanostructures using only short synthetic DNA strands, with potential applications in various fields such as nanotechnology, biophysics, and bioimaging.The authors describe a novel method for constructing complex three-dimensional (3D) structures using short synthetic DNA strands, referred to as "DNA bricks." Each DNA brick is a 32-nucleotide single-strand with four 8-base binding domains, allowing it to bind to four neighbors and form a modular component. In one-step annealing reactions, these bricks self-assemble into prescribed 3D shapes without the need for a scaffold strand. The modular nature of the method allows for the construction of 102 distinct shapes with intricate features, including solid shapes with sophisticated geometries and surface patterns, as well as hollow shapes with tunnels and cavities. The authors also demonstrate the versatility of the method by constructing structures with alternative packing geometries and using non-canonical brick motifs. This work establishes DNA bricks as a robust and versatile framework for creating complex 3D nanostructures using only short synthetic DNA strands, with potential applications in various fields such as nanotechnology, biophysics, and bioimaging.