In 2015, the 1st commercial nanopore DNA sequencing device was launched by Oxford Nanopore Technologies. Mostly based on a synthetically engineered transmembrane protein, nanopore sequencing permits long DNA strands to be channeled by means of the central lumen of the pore where modifications within the ionic current work as a sensor of the individual bases within the DNA. This method was a key milestone for DNA sequencing, and the achievement has been only made possible after decades of research.
Since then, researchers have tried to extend this principle and build bigger pores to accommodate proteins for sensing purposes; however, the main problem has been the restricted understanding of artificial protein design. Instead, a new method based on artificial folding of DNA into complex structures, the so-referred to as 3-D-origami technique, first reported by the AU group in 2009, has emerged. In comparison with proteins, DNA origami has been proven to have an unprecedented design space for constructing nanostructures that mimic and extend naturally occurring complexes.
In a new article, revealed in Nature Communications, the researchers now report the creation of a large synthetic nanopore produced from DNA. This nanopore structure is able to translocate large protein-sized macromolecules between compartments separated by a lipid bilayer. As well as, a functional gating system was introduced contained in the pore to allow biosensing of only a few molecules in solution.
Lastly, the pore was provided with a set of controllable flaps, permitting targeted insertion into membranes displaying specific signal molecules. In the future, this mechanism will potentially allow the insertion of the sensor specifically into diseased cells and will permit diagnosis on the single-cell level.