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Building Nanoscale Structures using DNA Origami

Idea Proposed

“moDON” – a modular DNA origami unit that can be reconfigured into a vast number of unique monomers (up to 59,049 variants) using a single set of DNA staples. Essentially, it’s a method for creating fully addressable, designer superstructures at the nanoscale. The work combines two distinct connection strategies (in-plane “xy” and out-of-plane “z”) to form larger, more complex assemblies than conventional DNA origami allows.

How It Works

  1. Modular Design:
    • XY-Direction: Modularity is achieved by re-routing the DNA scaffold to create shape-complementary connection sites (protrusions and indentations). These sites are designed to be specific, allowing multiple moDON units to assemble into defined planar (2D) superstructures.
    • Z-Direction: A three-strand connection system is used to connect moDONs in the third dimension. Here, directional DNA handles and connector strands allow the formation of robust, non-branching connections between layers.
  2. Assembly and Disassembly:
    • Assembly Triggers: High concentrations of MgCl₂ promote the xy-assembly by stabilizing the DNA duplexes, while the addition of specific connector strands triggers z-assembly.
    • Controlled Disassembly: The system can be disassembled selectively. For example, toehold-mediated strand displacement is used to remove the z-connectors, and lowering the MgCl₂ concentration can disassemble xy-connections. This orthogonality allows for dynamic control over the structure.

How You Can Use This

  • Research and Development: Use the modular design to create custom nanoscale structures for applications in sensing, molecular electronics, or as scaffolds for functional molecules.
  • Synthetic Biology: The approach offers a way to build cytoskeleton-like structures or reconfigurable platforms that can dynamically assemble and disassemble, which is valuable for mimicking biological systems or for drug delivery platforms.
  • Cost-Effective Nanofabrication: By using a single set of staples to generate thousands of unique monomers, this method significantly reduces the design and production cost compared to traditional DNA origami techniques.
  • Educational and Exploratory Applications: The paper can serve as a basis for further studies in DNA nanotechnology, providing insights into hierarchical assembly, structural addressability, and dynamic control at the nanoscale.

Sources & citation

Weck, J.M., Heuer-Jungemann, A. Fully addressable designer superstructures assembled from one single modular DNA origami. Nat Commun 16, 1556 (2025). https://doi.org/10.1038/s41467-025-56846-2