Folding Double-Stranded DNA into Designed Shapes with Triplex-Forming Oligonucleotides

Cindy Ng, Anirban Samanta, Ole Aalund Mandrup, Emily Tsang, Sarah Youssef, Lasse Hyldgaard Klausen, Mingdong Dong, Minke A.D. Nijenhuis*, Kurt V. Gothelf*

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

The compaction and organization of genomic DNA is a central mechanism in eukaryotic cells, but engineered architectural control over double-stranded DNA (dsDNA) is notably challenging. Here, long dsDNA templates are folded into designed shapes via triplex-mediated self-assembly. Triplex-forming oligonucleotides (TFOs) bind purines in dsDNA via normal or reverse Hoogsteen interactions. In the triplex origami methodology, these non-canonical interactions are programmed to compact dsDNA (linear or plasmid) into well-defined objects, which demonstrate a variety of structural features: hollow and raster-filled, single- and multi-layered, with custom curvatures and geometries, and featuring lattice-free, square-, or honeycomb-pleated internal arrangements. Surprisingly, the length of integrated and free-standing dsDNA loops can be modulated with near-perfect efficiency; from hundreds down to only six bp (2 nm). The inherent rigidity of dsDNA promotes structural robustness and non-periodic structures of almost 25.000 nt are therefore formed with fewer unique starting materials, compared to other DNA-based self-assembly methods. Densely triplexed structures also resist degradation by DNase I. Triplex-mediated dsDNA folding is methodologically straightforward and orthogonal to Watson-Crick-based methods. Moreover, it enables unprecedented spatial control over dsDNA templates.

Original languageEnglish
Article number2302497
JournalAdvanced Materials
Volume35
Issue40
ISSN0935-9648
DOIs
Publication statusPublished - Oct 2023

Keywords

  • DNA nanotechnology
  • Hoogsteen
  • origami
  • self-assembly
  • triplex

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