The paper introduces caDNAno, an open-source software for designing 3D DNA-origami shapes constrained to a honeycomb lattice. The software simplifies the design process by providing a graphical user interface and tools for creating and analyzing DNA sequences. The authors designed seven different rectangular-block motifs, identifying a well-behaved motif suitable for future studies. The software significantly reduces the effort required to design 3D DNA-origami structures, with example designs and video tutorials available online. DNA origami, a method for constructing arbitrary 2D shapes, has been extended to 3D shapes. The authors developed caDNAno to assist in the design of these structures, reducing the complexity of the design process. The software allows users to force crossovers between any two staple or scaffold bases, though care must be taken to avoid folding failures due to deviations from canonical DNA geometry. The design process involves four main steps: selecting a scaffold path, assigning staple paths, breaking staple paths into shorter segments, and applying a DNA sequence to the scaffold. The caDNAno interface includes three panels for visualizing and editing the design: Slice, Path, and Render. The Slice panel provides an x-y cross-section view of the honeycomb lattice, the Path panel allows nucleotide-level editing of scaffold and staple paths, and the Render panel provides a real-time 3D model of the design. The authors used caDNAno to design seven different honeycomb-pleated-origami rectangular blocks, varying in the number of rows and helices per row. The results showed that the six-helix-per-x-raster design produced the most robust and well-folded structures. The software is available at http://cadnano.org/, with example designs and video tutorials. The source code is released under the MIT license. The study highlights the potential of caDNAno in accelerating the design and fabrication of complex 3D DNA nanostructures.The paper introduces caDNAno, an open-source software for designing 3D DNA-origami shapes constrained to a honeycomb lattice. The software simplifies the design process by providing a graphical user interface and tools for creating and analyzing DNA sequences. The authors designed seven different rectangular-block motifs, identifying a well-behaved motif suitable for future studies. The software significantly reduces the effort required to design 3D DNA-origami structures, with example designs and video tutorials available online. DNA origami, a method for constructing arbitrary 2D shapes, has been extended to 3D shapes. The authors developed caDNAno to assist in the design of these structures, reducing the complexity of the design process. The software allows users to force crossovers between any two staple or scaffold bases, though care must be taken to avoid folding failures due to deviations from canonical DNA geometry. The design process involves four main steps: selecting a scaffold path, assigning staple paths, breaking staple paths into shorter segments, and applying a DNA sequence to the scaffold. The caDNAno interface includes three panels for visualizing and editing the design: Slice, Path, and Render. The Slice panel provides an x-y cross-section view of the honeycomb lattice, the Path panel allows nucleotide-level editing of scaffold and staple paths, and the Render panel provides a real-time 3D model of the design. The authors used caDNAno to design seven different honeycomb-pleated-origami rectangular blocks, varying in the number of rows and helices per row. The results showed that the six-helix-per-x-raster design produced the most robust and well-folded structures. The software is available at http://cadnano.org/, with example designs and video tutorials. The source code is released under the MIT license. The study highlights the potential of caDNAno in accelerating the design and fabrication of complex 3D DNA nanostructures.