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

TY - JOUR

T1 - Folding Double-Stranded DNA into Designed Shapes with Triplex-Forming Oligonucleotides

AU - Ng, Cindy

AU - Samanta, Anirban

AU - Mandrup, Ole Aalund

AU - Tsang, Emily

AU - Youssef, Sarah

AU - Klausen, Lasse Hyldgaard

AU - Dong, Mingdong

AU - Nijenhuis, Minke A.D.

AU - Gothelf, Kurt V.

N1 - Publisher Copyright: © 2023 The Authors. Advanced Materials published by Wiley-VCH GmbH.

PY - 2023/10

Y1 - 2023/10

N2 - 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.

AB - 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.

KW - DNA nanotechnology

KW - Hoogsteen

KW - origami

KW - self-assembly

KW - triplex

UR - http://www.scopus.com/inward/record.url?scp=85165873776&partnerID=8YFLogxK

U2 - 10.1002/adma.202302497

DO - 10.1002/adma.202302497

M3 - Journal article

C2 - 37311656

AN - SCOPUS:85165873776

SN - 0935-9648

VL - 35

JO - Advanced Materials

JF - Advanced Materials

IS - 40

M1 - 2302497

ER -