DNA origami is a method to make custom-shaped DNA assemblies at the nanoscale. These DNA assemblies have been used as smart cancer vaccines, molecular rules, and light harvesters, showcasing the potential of this material class. DNA origami nanostructures are made by mixing a long single-stranded DNA ‘scaffold’ with short single-stranded DNA ‘staples’ and letting the mixture self-assemble into a pre-determined shape.
The Bathe lab at MIT, with collaborators at Baylor University and Arizona State University, published a paper in Science describing the top-down design of DNA origami. Designing DNA origami shapes used to require field expertise and long hours of design. With this advance, anyone could acquire the scaffold and staple DNA sequences for an arbitrary polyhedral shape.
Last year, the Bathe lab collaborated with the Irvine Lab (MIT) and Schief Lab (Scripps) to apply this new material platform. This research, published in Nature Nanotechnology, attached clinically relevant HIV antigens onto the DNA origami to determine the nanoscale rules around how B-cells (immune cells that create antibodies) recognize antigens.
The method used to attach the antigens to the DNA origami is limited to specific contexts. For example, this method would not be useful for attaching a carbohydrate molecule onto the nanostructure. In a new paper in ACS Nano, the Bathe group present a new method for attaching molecules to DNA origami. We utilize ‘click chemistry’ to attach proteins, peptides, carbohydrates, dyes, and polymers onto the DNA origami, highlighting the generality of this approach. In addition, we develop a characterization tool to accurately measure how many molecules are attached to a given nanostructure. We demonstrate that this new attachment method behaves similarly to the old method when interacting with B-cells.
Future work will investigate whether this new attachment method behaves differently in mice. In addition, with the ability to generate DNA nanostructures with different sizes, shapes, and now functionality, we envision generating libraries of nanoparticles for vaccine and genetic therapy applications.