Biodesign Institute’s constructions include spheres, ellipsoids, and a round-bottomed DNA nanoflask.

Scientists have developed a modified DNA origami technology for constructing complex 3-D DNA nanostructures. The technique, reported by Hao Yan, Ph.D., Yan Liu, Ph.D., graduate student Dongran Han, and colleagues at Arizona State University’s Biodesign Institute, has allowed the generation of closed 3-D DNA structures with curved surfaces including spheres and ellipsoid shells.

The team reports that it has also produced a round-bottomed DNA nanoflask, the structure of which has been captured by transmission electron microscopy. The achievement is reported in Science in a paper titled “DNA Origami with Complex Curvatures in Three-Dimensional Space.”

DNA nanotechnology can now be used to assemble structures with a variety of geometric shapes, the researchers write. The technology is founded on the basic ability to bring together a series of DNA double helices arranged with their helical axes parallel to one another and hold the structure together with crossovers between neighboring helices.

Generating simple, angular 3-D structures using an origami approach involves holding a scaffold of single-stranded section of DNA in the right shape using numerous short single strands of DNA (staples) and then filling in the structure with short segments of double-stranded DNA “pixels” arranged in parallel. The most successful techniques have allowed researchers to generate geometric DNA nanostructures such as hollow polygons and densely packed cuboids.

One of the major limiting factors in the process, however, is that placement of the crossover points must fall within the pre-existing structural characteristics of B-form DNA. Conventional, block-based DNA origami designs can’t be fine-tuned in terms of detail, the Biodesign Institute researchers add. “As with all finite pixel-based techniques, rounded elements are approximated, and intricate details are often lost”.

Attempts have been made to construct relatively complex 3-D DNA origami nanostructures that contain some degree of curvature. One approach is based on the targeted insertion and deletion of base pairs in selected segments within a 3-D building block comprising a tightly cross-linked bundle of helices. However, the researchers note, “it remains a daunting task to engineer subtle curvatures on a 3-D surface.”

In order to meet the challenge of modeling DNA to mimic the more curved 3-D shapes found in nature, and in particularly in biological molecules, Drs. Yan and Liu and their team set out to develop design principles that would allow researchers to more accurately control the degree of surface curvature.

Moving away from the rigid lattice model, the new strategy involves first defining the desired surface features of a target object using a scaffold and then manipulating the DNA conformation and shaping of crossover networks to achieve the design. Demonstrating the principle of their approach, the researchers constructed a series of concentric 2-D ring structures, each of which is formed from a DNA double helix.

The rings are bound together using strategically placed crossover points, where one of the strands in a given double helix stitches to an adjacent ring. By varying the number of nucleotides between crossover points and the position of crossovers within the structure, a range of both sharp and rounded elements could be constructed in a 2-D form. The Arizona team’s constructions included an opened nine-layer ring and a three-pointed star.

Designing more complex 3-D structures with finely tuned in-plane and out-of-plane curvatures was then achieved by manipulating the crossover points further and wrapping the structure up in a length of DNA scaffold. Even using this concentric ring approach the range of curvature achievable should still be limited because standard B form DNA will not tolerate large deviations from its preferred configuration of 10.5 base pairs/turn, the authors note.

Dr. Yan recognized that slightly over- or under-twisting the helices could, however, produce different bending angles. Combining concentric helices with such non-B-form DNA (that has 9–12 base pairs/turn), the group found they could produce sophisticated 3-D shapes.

The researchers are working to expand the range of nanoforms that can be generated using their approach. They admit, though, that the more elaborate structures will need even longer lengths of single-stranded DNA scaffolding. In the long term they hope the technology will pave the way to the design of nanoscale biomedical tools such as drug-releasing nanospheres or nanoreactors for biochemical reactions.

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