inSēquio: A Programmable 3D CAD Application for Designing DNA Nanostructures

Abstract

DNA nanotechnology is evolving rapidly, paralleling the historic trajectory of the 1970s electronics industry. However, current DNA nanostructure (DN) design software limits users to either manual design with minimal automation or a constrained range of automated designs. inSēquio Design Studio, developed by Parabon® NanoLabs, bridges this gap as a programmable 3D computer-aided design (CAD) application, integrating a domain-specific graphical editor with a Python API for versatile DN design. Developed in C++ for Windows® and Macintosh® systems, inSēquio features a user-friendly graphical user interface with extensive CAD tools, capable of managing complex designs and offloading computational tasks to the cloud. It supports various DNA design formats, PDB molecule integration, residue modifications, and includes preloaded designs and thorough documentation. With its combination of features, inSēquio enables a code-centric design (CCD) approach, enhancing DN construction with improved precision, scalability, and efficiency. This approach is elucidated through a streptavidin barrel cage designed via Python notebook and a spheroid origami case study. Marking a significant advance in DN design automation, inSēquio, the first fully programmable 3D CAD tool for DN design, enables both manual and programmatic 3D editing. This fusion of features establishes inSēquio as a transformative tool, poised to significantly enhance designer productivity and expand the scope of possible designs.