A computational framework for designing micron-scale crisscross DNA megastructures.

Authors

Matthew Aquilina, Florian Katzmeier, Minke A D Nijenhuis, Siyuan Stella Wang, Corey Becker, Yichen Zhao, Su Hyun Seok, Julie Finkel, Huangchen Cui, Jaewon Lee, Seungwoo Lee, William M Shih

Published in

Nature communications. Jul 17, 2026. Epub Jul 17, 2026.

Abstract

Crisscross polymerization enables the assembly of hundreds of unique DNA origami 'slats' into micron-sized structures with nanoscale precision. To design these megastructures, thousands of handle sequences from a fixed library must be assigned to individual slats to encode the desired binding architecture. This complexity presents two major challenges: handles must be selected to minimize parasitic interactions that compete with desired assembly, and the fabrication of hundreds of unique slats creates a substantial logistical burden. Here, we develop a unified framework that standardizes the design and fabrication of crisscross megastructures. We use an evolutionary algorithm to optimize handle assignment and minimize parasitic binding between slats. Together with an expanded handle library, the algorithm enables the assembly of large, multi-layered megastructures that otherwise would be produced at negligible yields. We have released this framework as #-CAD, an open-source graphical application that integrates these algorithms, streamlines laboratory workflows, and makes crisscross DNA origami more broadly accessible.

PMID:
42469232
Bibliographic data and abstract were imported from PubMed on 18 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.