Further progress in the miniaturization of technology will depend on our ability to finely control the organization of matter on a molecular scale. A key property of DNA -- its ability to be copied and amplified by polymerases -- allows for the exploration of DNA sequence space through directed molecular evolution, one of the most powerful tools in molecular design. Unfortunately, DNA objects as they are currently designed incorporate knots and catenations, which render them unreplicable using simple polymerization. This problem can be bypassed by encoding DNA objects as long single strands that are programmed to fold into a branched-tree structure. Each terminal branch is further programmed to complete an edge of the object by forming a noncovalent bridge with a specific intramolecular partner terminal branch. Unlike with knotted or catenated systems, replication of these objects by polymerases does not require covalent bond breakage and formation. As proof of principle, a 1.7-kilobase single-stranded DNA was constructed that is replicable by polymerases and that, in the presence of five 40mer oligonucleotides, can be folded into a wireframe regular octahedron structure by a simple denaturation-renaturation procedure. The resulting octahedron, approximately 22 nanometers on a side, was visualized by cryo-electron microscopy and shown to have the predicted structure.

References and Footnotes

1. Shih, W. M., Quispe, J. D., and Joyce, G. F. Nature 427, 618?621 (2004).