“Building complex three-dimensional DNA wireframes directly from synthetic oligonucleotides (as has been done in the past) is a very time-consuming and inefficient process, and thus not practical for many applications,” researcher William Shih told nanotechweb.org. “We sought to build the biomimetic way, with a single long polymer that folds back on itself, using non-covalent interactions, to form a complicated three-dimensional structure.”

The 1669-nucleotide DNA molecule folded up in the presence of five 40-nucleotide synthetic oligodeoxynucleotides by a simple denaturation-renaturation process caused by heating and a series of cooling steps. The resulting octahedral structure had a central cavity capable of holding a sphere 14 nm in diameter, while the triangular opening on each face of the octahedron could let through a sphere up to 8 nm in diameter.

“Our DNA octahedron is the first rigid DNA nanostructure that is clonable, i.e. can be copied by polymerases - biomolecular machines that can copy and amplify given sequences,” said Shih. “Our strategy can be generalized for the design of other amplifiable DNA nanostructures. Polymerases could also facilitate the discovery of novel single strand encoded DNA molecular machines through the procedure known as directed molecular evolution.”

Shih says that three-dimensional arrays of the DNA octahedra could be used to image guest molecules inserted into the lattice, or for organizing molecular-scale logic gates into complex three-dimensional circuits for molecular computing applications. “Two key challenges are the reliable assembly of DNA octahedra into three-dimensional networks and the reliable attachment of guest macromolecules to the octahedra,” he added.

According to Shih, the octahedra could also find use as a cage to trap molecules and protect them from the outside environment, perhaps being programmed to release their contents in response to a signal. This would require the design of molecular “caps” to seal off the open faces of the octahedron, and strategies for the reversible capture of guest molecules.

“Directed evolution could be used for attempts to develop complex mechanical behaviour from DNA loops organized by an octahedron scaffold,” continued Shih. “This could lead to custom molecular machines reminiscent of those found in nature - for example, molecular assemblers and disassemblers such as chaperones or polymerase clamp loaders. Directed evolution has already been used successfully to discover static and even allosterically controlled catalysts. It would be a great feat to evolve more complicated molecular machines, and amplifiable DNA nano-scaffolds could play a key role in meeting this challenge.”

The researchers reported their work in Nature.