DNA Origami Nanopores: An Emerging Tool in Biomedicine

Abstract

Natural systems have developed a precise and intricate machinery to preserve life. The com­ plex mechanisms that living organisms employ to control the transport of ions and mole­ cules across their lipid membranes represent a remarkable example. Membrane transport is of indisputable importance, as it is ultimately implicated in such important functions as energy production and protein synthesis. Many transport pathways are mediated by the pres­ ence of small holes (known as nanopores in biotechnology) in the lipid membranes based on active or passive proteins. Since living organ­ isms so efficiently utilize these protein­based holes in their membranes to control the passage of biomolecules, why not employ them to obtain devices with potential interest in biotechnology and biomedicine? A key achievement in biotechnology was the detection of single molecules utilizing nano­ pores. Two decades ago, Kasianowicz et al. [1] were able to detect single DNA and RNA mol­ ecules for the first time using a natural nano­ pore (a­hemolysin) inserted into an artificial lipid membrane by means of the resistive pulse technique [2]. The idea is easy and elegant: indi­ vidual molecules pass through a nanopore lead­ ing to changes in the ionic current characteristic of the translocating molecule. a­hemolysin (a Staphylococcus aureus pore­ forming protein) has been by far the most employed biological pore due to its dimensions, stability and commercial availability. The main advantage of using these biological pores is their perfectly defined structure, which guar­ antees reproducibility of measurements and the possibility of introducing different chemi­ cal groups by mutating the DNA sequence of the protein pore. This can be used to increase