DNA nanocages: Self-assembly and potential applications

In bionanotechnology, DNA has been shown as a superb molecular system in self-assembly towards bottom-up nanofabrication. In the last three decades, a range of DNA motifs have been developed and sophisticated one-, two- and three-dimensional (1, 2 and 3D) DNA nanostructures have been fabricated. These DNA complexes have well-characterized structures and excellent capabilities for molecular recognition, which endow them with promising applications as templates in nanofabrications, sensing materials in diagnostics, and logic units in molecular computations. My major researches focus on developing a general method to assemble DNA nanocages and also apply them as organizational scaffolds. DNA 3D nanostructures draw great attentions because their sizes and morphologies can be potentially programmed to fit interactions with viruses or other biological organelles. However, reported 3D geometric DNA structures are sparse and require tedious works. During my research, we developed a general approach to use “branched symmetric motifs” as building blocks in self-assembly of DNA 3D nanostructures. This approach mimics the assembly of spherical viral capsids. Several factors can be used to control the morphologies of final products, such as branched arm number, the flexibility and concentration of the motifs. When carefully balancing the flexibilities and the rigidities of the motifs and controlling the DNA concentrations, a range of geometrically well-defined polyhehedra including tetrahedra, octahedra, cubes, icosahedra and large spherical nanocages can be assembled from different star-shaped DNA motifs. In addition, the asymmetric DNA motifs were investigated as new building blocks, which broaden the DNA self-assembled structures. In my research, the asymmetric Y motifs were successfully applied to construct the DNA triangular prisms. Beyond the new structure assemblies, the asymmetric free linkage loops were also introduced in the central strand, resulting in well control of the chirality of DNA triangular prisms. Besides the fabrication process, I am exploring potential applications of the DNA star-shaped motifs. Various star-shaped DNA motifs modified with folic acid at the branch ends were assembled to test the affinity to the folate receptors and the endocytosis to cancer cells. Experiments reveal that cancer cells have different binding affinities to varied star-shaped motifs, indicating the folate receptors on cell surfaces prefer the three fold distribution of the ligands, which usually show the highest binding affinity