Introduction

DNA origami is a process by which a researcher can create nano-scale structures using DNA as a building material. DNA origami was developed by Paul W. K. Rothemund of Caltech. It works by using a long "scaffold" strand of viral DNA and holding it together using short, 200-250 base, "staple strands." The origami is formed by a researcher using enzymes to cut DNA in certain places on a 5,000-10,000 base strand, inducing the cut pieces into parallel positions and making crossovers, and then using the staple strands to strengthen the structure.1

History

The use of DNA as a building material for nano-structures was first put forth by Nadrian Seeman in 1982.2 In his article, “Nucleic Acid Junctions and Lattices,” Seeman suggests that due to the principles of base-pairing and the presence of “replicational junctions” might allow for the construction of three dimensional shapes.3 Previously, there was more of a focus on build nano structures by directing working with atoms using various forms of microscopy. These methods were and continue to be very expensive to use, so many scientists turned to looking for biological nano-structures that would self-assemble. That was some success in this field, but the usual methods usual involved sheets of short interlocking strands. This kind of structure required many steps to create, as even a small miscalculation in ratios could lead to the whole process failing. The main breakthrough came when one researcher folded one strand of DNA to create a single structure. Paul W.K. Rothemund built on this idea and combined the two methods: Folding one long strand of DNA and then using staple stands to strengthen the structure.

Rothemund Method

The construction of a DNA origami nanostructure begins with a 7,000-bp strand of DNA, called a scaffold strand. Often, the scaffold strand is genome of a virus. To complete the helices needed to create DNA origami, small “staple strands” of roughly 200-bp are mixed with the scaffold strain and annealed. The staple strands are cut from a larger strand using restriction enzymes. The cutting is done is such a way that the staples will bind at specific points on the scaffold strand.

A computer program is used by a researcher to design the folding needed to create the desired shape. This folding structure will be held together by a set of crossovers: places where either the scaffold strand or a staple strain is switched between two helices.

Advances in Origami Modelling

In 2009, a group of researchers published an article in which they explained how they built on Rothemund’s method in order to create three dimensional structures.2

Applications

Since the introduction of DNA origami in 2006 there has been special interest in using the technology to create nanostructures that can deliver medicine to target regions, and even specific cells, within the body. Now that it is possible to create three-dimensional DNA origami, these structures provide a very adaptable and biocompatible delivery system. As modeling programs and synthesis technics improve, more and more detailed structures will allow for doctors and researchers to precisely adjust certain features, such as the release rate of structure contents. In one study, it was shown that DNA origami structures laced with doxorubicin, a powerful cancer drug, were extremely effective at killing tumor cells that had previously developed a resistance to the drug.3 The researchers suggest that their DNA nanostructures were ability to circumvent the drug resistance of these cancer cells by “…increasing the cellular uptake of doxorubicin and inducing a change in lysosomal pH that [redistributed] the drug to target sites.”3

Current Research

Conclusion

In the future, this technology could become a mainstay of most medical fields and beyond. With the ability to be easily redesigned, DNA origami could even help combat disease like MRSA that are notorious for quickly developing drug resistance.