A Comprehensive Review of DNA Origami Stabilization Techniques

In recent years, DNA has emerged as a powerful tool in the field of nanotechnology. The DNA origami technique is largely responsible for this, revolutionizing nanofabrication due to its controllability, precision, and ability to leverage DNA’s unique properties. The technique consists of folding a long, single-stranded DNA (called a scaffold strand) by binding it with shorter staple strands to create almost any shape desired. With a desired structure in mind, researchers can design and assemble scaffold and staple strands using computer software like Cadnano or Tiamat. This is possible because of the Watson-Crick base pairing of DNA strands, which allows for programmable self-assembly of DNA nanostructures and therefore, the synthesis of arbitrary 2D and 3D shapes. Because DNA is a biomolecule,the nanostructures are also biocompatible and can be employed in biological applications including drug delivery. DNA origami nanostructures are not only limited to biological applications; they have also found uses in nanophotonics, plasmonics, and electronics. However, DNA origami still faces many challenges before it can be widely adopted. One such challenge is ensuring stability, and thus guaranteeing the performance of the DNA origami, in the presence of heat, nuclease in organic bodies, and chaotropic agents. This warrants the question: what methodologies can be employed to best stabilize DNA origami structures? This paper further focuses on two methods: covalently binding various molecules by cross-linking and non-binding encapsulation. Detailed analysis and comparison between various molecules used to bind and coat DNA nanostructures is used to evaluate performance and applicability of each method. In the end an oligolysines coating cross-linked with glutaraldehyde was found to have the strongest biological stability, thymine cross-linking had the strongest thermal stability, a silica coating had the best stability against the largest number of factors, and both graphene and Al3O2 coatings had the best mechanical stability.