Triplex-forming oligonucleotides: a third strand for DNA nanotechnology

Abstract

DNA self-assembly has proved to be a useful bottom-up strategy for the construction of user-defined nanoscale objects, lattices and devices. The design of these structures has largely relied on exploiting simple base pairing rules and the formation of double-helical domains as secondary structural elements. However, other helical forms involving specific non-canonical base-base interactions have introduced a novel paradigm into the process of engineering with DNA. The most notable of these is a three-stranded complex generated by the binding of a third strand within the duplex major groove, generating a triple-helical (‘triplex’) structure. The sequence, structural and assembly requirements that differentiate triplexes from their duplex counterparts has allowed the design of nanostructures for both dynamic and/or structural purposes, as well as a means to target non-nucleic acid components to precise locations within a nanostructure scaffold. Here, we review the properties of triplexes that have proved useful in the engineering of DNA nanostructures, with an emphasis on applications that hitherto have not been possible by duplex formation alone.

Substitution‐Inert Polynuclear Platinum Complexes That Inhibit the Activity of DNA Polymerase in Triplex‐Forming Templates

“…[8] Notably, DNA triplexes have been also proved useful in the development of DNA-based nanostructures and materials. [9] …”

A Molecular Hero Suit for In Vitro and In Vivo DNA Nanostructures

“…For example, DNA boxes with lids containing i‐motif interactions can be closed or opened using pH changes . Another pH‐sensitive element is triple helical DNA . Assembly of 3‐point‐star motifs into a DNA tetrahedron is stabilized by triplex formation at pH 5; the interactions become weaker at pH 8 when the triplex forming strand dissociates, thus breaking open the tetrahedron .…”

“…Adding such functionalities to DNA nanostructures is possible due to the different types of chemistries now available; some of these have even been commercialized. Postassembly functionalization of DNA nanostructures is also possible through sequence specific recognition or click chemistry . Control of these nanostructures by external factors such as light provides spatial and temporal regulation of these drug carriers in living systems .…”

Exceptional biostability of paranemic crossover (PX) DNA, crossover-dependent nuclease resistance, and implications for DNA nanotechnology

“…While this is notably incorrect, there are instances both in biology and biotechnology where DNA structures can have more than two strands. Triplexes, for example can form a single helix using three strands, 1 while guanine tetrads can form four-stranded DNA complexes. 2 In DNA nanotechnology, synthetic DNA strands are designed and integrated together to form different motifs that serve as the building blocks for bottom-up construction.…”