DNA Nanostructures By Design

In what some researchers are calling a seminal achievement, a group of scientists have succeeded in creating self-assembled crystalline DNA structures in three dimensions.

Two-dimensional architectures had been devised before, but the new assemblies are the first designed 3-D DNA structures. Such rationally designed crystals, for decades envisioned as controllable nanotechnological frameworks, have innumerable potential uses—including as scaffolds for determining crystallographic structures of biomolecules and as components for circuits and electronic devices.

New York University chemistry professor Nadrian C. (Ned) Seeman, Purdue University chemistry professor Chengde Mao, and their colleagues have produced macroscopic 250-μm DNA crystals, which they were able to resolve at 4 Å by X-ray crystallography (Nature 2009, 461, 74).

The work represents “landmark progress” in the field of designed DNA, says Caltech computer scientist Paul W. K. Rothemund, whose lab uses a technique called DNA origami to fold DNA into 2-D structures. Thomas LaBean, a professor at Duke University who specializes in DNA nanostructure design, calls the study a “crucial milestone.”

In principle, double-stranded DNA, with its predictable base-pair affinities that make controlled binding possible, serves as an ideal template for structure design. But achieving such designs with the necessary nanometer-scale precision has proved difficult.

Design of 2-D DNA structures is well established. Seeman’s group had recently been on the verge of success in creating 3-D crystals, but the specimens still had some problems that prevented the researchers from obtaining X-ray crystallographic images with sufficient resolution. With this new work, however, “Ned can feel comfortable declaring victory,” Rothemund says.

The group makes use of what they call “tensegrity triangles,” rigid 3-D triangular units consisting of three connected non-coplanar double helices of DNA. The ends are “sticky,” in that some strand ends are a few bases longer than others, leaving them ready to bond with another end bearing complementary base pairs. By forming such links, the group constructed a symmetric 3-D lattice.

Seeman’s group now aims to design crystals with larger unit cells and less symmetry.

LaBean says that he believes “this type of periodic molecular material will live up to its technological promise.”