Future | YOKABIO2024

We have designed a DNA structure called “KIT-D” that allows for the creation of various nanoscale tube shapes through different combinations of hinges and latches. This structure enables control over the inner diameter and length, which can be adjusted to create stable configurations when the latch is engaged, compared to a more flexible configuration when the latch is released. In the future, we envision utilizing “diameter variation” and “length variation” to tailor these structures into longer or shorter configurations with distinct roles. Below are some specific application examples.

Figure 1. Multi Structure

However, there are problems with this, such as the increase in the number of control points making the overall control more complicated, and the increase in connecting parts requiring more careful design in terms of ensuring the stability of the structure.

Application focused on changes in inside diameter

Secondly, focusing on the feature of diameter variation, an application as a “molecular filtering system” is possible. By adjusting the angle of the hinge, this structure allows changes in inner diameter, enabling selective capture and filtration of specific molecules. This has potential applications in biomarker separation and drug purification.

Figure 2. Change in inner diameter due to structural change

A technical challenge here is the limitation on maximum diameter. Since the structure size is constrained by DNA origami, expanding the usable diameter remains an area for further development to broaden the range of applicable molecule sizes.

Transformations responsive to a variety of stimuli

One possible way to further improve KIT-D is to modify the trigger mechanism for the gating function. Currently, a chain exchange reaction using single-stranded DNA (ssDNA) is used, but by replacing this with a pH-responsive i-motif[1], an ion-responsive G-quadruplex, or a photoresponsive azobenzene-based chain exchange reaction, it will be possible to change the structure in response to external stimuli such as pH, ion concentration, and light, respectively. Ultimately, it may be possible to realize a structure that changes its structure in response to stimuli in a nanoscale environment and functions as a nanopore that selectively passes substances through.

Figure 3. Trigger Mechanism Applications

One issue with this application is sensitivity as a sensor. With the current structural transformation mechanism, deformation does not occur unless all triggers are activated. To increase sensitivity, further adjustments are necessary, such as miniaturizing the overall structure and positioning the sensors closer together.