Weave Tile Architecture Construction Strategy for DNA Nanotechnology

Abstract

Architectural designs for DNA nanostructures typically fall within one of two broad categories: tile-based designs (assembled from chemically synthesized oligonucleotides) and origami designs (woven structures employing a biological scaffold strand and synthetic staple strands). Both previous designs typically contain many Holliday-type multi-arm junctions. Here we describe the design, implementation, and testing of a unique architectural strategy incorporating some aspects of each of the two previous design categories but without multi-arm junction motifs. Goals for the new design were to use only chemically synthesized DNA, to minimize the number of component strands, and to mimic the back-and-forth, woven strand routing of the origami architectures. The resulting architectural strategy employs "weave tiles" formed from only two oligonucleotides as basic building blocks, thus decreasing the burden of matching multiple strand stoichiometries compared to previous tile-based architectures and resulting in a structurally flexible tile. As an example application, we have shown that the four-helix weave tile can be used to increase the anticoagulant activity of thrombin-binding aptamers in vitro.

Through-bond effects in the ternary complexes of thrombin sandwiched by two DNA aptamers

“…Since the interaction of each aptamer is mediated by different protein sub-domains, it is possible to enhance their activity just by linking them together thus generating a bivalent aptamer with improved affinity and specificity (28–38). In particular, a relevant enhancement of functional affinity has been obtained by using linkers based on PEG-chains (32), randomized DNA sequences (36) or DNA weave tiles (33,37,38). …”

Folding of DNA origamis

“…These experiments clearly need to be improved, both to quantify the influence of the experimental conditions (quenching the structure or controlling the temperature without quenching) and the interaction with the surface (Song et al 2012). Extensions to 3D Douglas et al 2009) and structures other than origami (Hansen et al 2010) are envisioned, as well as tests at the single molecule level (FRET). The inclusion of kinetic effects is also another aspect we would like to include, particularly in view of the recent results reported by Dietz's group (Sobzac et al 2012) showing the possibility to obtain almost defect-free origamis with very fast annealing protocols.…”

Structural DNA Nanotechnology: From Design to Applications

“…In another work, Hansen et al introduced a way to incorporate some features of both the origami method and the tile based self-assembly to produce weave tile structures [20]. They reported formation of flexible structures that were used to increase the anticoagulant activity of thrombin-binding aptamers.…”