Scaffolded DNA Origami: from Generalized Multicrossovers to Polygonal Networks

Abstract

My acquaintance with Ned Seeman began in the Caltech library sometime during 1992. At the time I was trying to design a DNA computer and was collecting papers in an attempt to learn all the biochemical tricks ever performed with DNA. Among the papers was Ned and Junghuei Chen's beautiful construction of a DNA cube [1]. I had no idea how to harness such a marvel for computation -the diagrams explaining the cube were in a visual language that I could not parse and its static structure, once formed, did not seem to allow further information processing. However, I was in awe of the cube and wondered what kind of mad and twisted genius had conjured it.Ned's DNA sculptures did turn out to have a relationship to computation. In 1994 Len Adleman's creation of a DNA computer [2] showed that linear DNA self-assembly, together with operations such as PCR, could tackle NP-complete computational problems. Excited by this result, Erik Winfree quickly forged an amazing link that showed how the self-assembly of geometrical DNA objects, alone, can perform universal computation [3]. The demonstration and exploration of this link has kept a small gaggle of computer scientists and mathematicians tangled up with Ned and his academic children for the last decade. At an intellectual level the technical achievements of the resulting collaborations and interactions have been significant, among them the first two-dimensional DNA crystals [4] and algorithmic self-assembly of both linear [5] and two-dimensional [6] arrays. By various other paths, a number of physicists have joined the party, mixing their own ideas with Ned's paradigm of "DNA as tinkertoys" to create nanomechanical systems such as DNA tweezers [7] and walkers [8,9,10]. DNA nanotechnology has taken on a life of its own since Ned's original vision of DNA fish flying in an extended Escherian lattice [11] and we look forward to a new "DNA world" in which an all-DNA "bacterium" wriggles, reproduces and computes.On a personal level, I and many others have gotten to find out exactly what kind of twisted genius Ned is. Ned is a singular character. He is at once gruff and caring, vulgar and articulate, stubborn and visionary. Ned is generous both with his knowledge of DNA and his knowledge of life. His

Designer nanoscale DNA assemblies programmed from the top down

“…S49 to S53). While these results mirror those for wireframe structures employing single-duplex edges (13), our use of DX-arms and multiway junctions here results in structurally stable, rigid assemblies that are crucial to most applications (10, 11). To test the utility of our objects for cellular assays, post-folding in TAE-Mg 2+ particles were transferred to PBS and Dulbecco's Modified Eagle's Medium (DMEM) containing 0 to 10% FBS, where they were found to be stable for at least 6 hours (Fig.…”

Conformational flexibility facilitates self-assembly of complex DNA nanostructures

“…Different potential strategies have been proposed. For example, based on his recently developed concept of ''DNA origami'', Paul Rothemund (26) has proposed the use of many DNA short strands to fold thousands-bases-long single DNA strands (i.e., M13 genomic DNA) into polyhedra. The idea is very interesting; however, its experimental realization remains elusive.…”

Nondeterministic polynomial time factoring in the tile assembly model

“…Rothemund has demonstrated what is currently the state-of-the-art of DNA nanostructure design and implementation with DNA origami, a concept of folding a single long scaffold strand into an arbitrary shape by using small helper strands [31,30,32]. Similar concepts may be the key to three-dimensional self-assembly, more powerful error-correction techniques, and self-assembly using biological molecules.…”

“…It is likely that their approach will require fewer tile types and perhaps assemble faster, but at the disadvantage of having to not only assemble crystals but also attach components to those crystals and create connections among those components. Nevertheless, Rothemund's work with using DNA as a scaffold may be useful in attaching and assembling such components [32].…”