The stringent base-pairing rules of DNA make it an exceptionally powerful bottom-up nanoscale material. DNA nanotechnology is a rapidly developing field, however, it suffers from the fact that it relies entirely on DNA duplex alignment as both a recognition and structural element. This limits structural versatility and introduces errors during self-assembly of DNA. In addition, current DNA nanomachines are based on transitions between DNA duplexes. To make the reactions unidirectional, duplexed substrates are designed to be thermodynamically less favorable than their respective product duplexes. Thus, the reactions are thermodynamically driven and, as a result, demonstrate detrimental background-activity. Guanine (G) quartets or quadruplexes show promise as an alternative to DNA duplexes. They have been proposed earlier as a potential tool for nanoscale assembly, however, formation of precisely defined quadruplexes is a significant challenge, because the G-quartets are formed by Gs only, which makes preventing slippage of the strands relative to each other problematic.
Recently, we have discovered a new way to build the monomolecular quadruplex of virtually infinite length employing GGGTGGGTGGGTGGG (G3T) segment as a monomeric unit. This tetrahelix has strictly determined self-assembly properties and represents promising material for both static and dynamic DNA nanotechnology. Monomolecular self-assembly eliminates errors characteristic of DNA duplex formation and allows very simple production of nanostructures through enzymatic replication (impractical for DNA duplexes due to topological constraints). Proposed nanomachines, based on DNA-to-quadruplex transition, can run without thermodynamic force, thereby eliminating undesired background activity. In conclusion, the proposed study can lift DNA nanotechnology to the next level by introducing monomolecular tetrahelix as a building material and driving force for nanomachines.