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Book of Abstracts: Albany 2005

category image Volume 22
No. 6
June 2005

A 1.7-kilobase Single-stranded DNA that Folds into a Nanoscale Octahedron

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).

William M. Shih1,*
Joel D. Quispe2
Gerald F. Joyce3

1Biological Chemistry and Molecular Pharmacology
Harvard Medical School
Cancer Biology
Dana-Farber Cancer Institute
44 Binney St.
Boston, MA 02115
2Cell Biology
The Scripps Research Institute
10550 North Torrey Pines Road
La Jolla, CA 92037
3Chemistry and Molecular Biology
The Skaggs Institute for Chemical Biology
The Scripps Research Institute
10550 North Torrey Pines Road
La Jolla, CA 92037

*Phone: 617 632 5143
Fax: 617 632 4471
Email: William_Shih@dfci.harvard.edu