Curvature controlled self-limited assembly using DNA origami building blocks

Our long-term goal is to design self-limited structures on length scales many times larger than the building blocks themselves. This project aims to construct large capsids with a high yield using a minimal number of building blocks. It is inspired by the ability of large viruses to form complete, functional capsids using very few components. Most of the smaller spherical viruses build icosahedral capsids to protect their genetic material, which can be explained by Caspar and Klug's theory of quasi-equivalence (1962). However, larger viruses like herpes simplex virus (T = 16) are built in layers. The inner layer is a type of vesicle comprising proteins around which the outer layer of protein subunits assembles into a highly symmetric icosahedral shape. Here, we describe an experimental strategy to mimic this design strategy using lipid vesicles as the inner layer and triangular building blocks (size ~ 50 nm) made of DNA origami for the outer layer. Our engineered triangular subunits are able to self-assemble on the vesicle surface with the help of cholesterol-modified DNA. Instead of using T = 16 quasi-equivalent interactions, as required by the Caspar-Klug paradigm, we use a spherical template to assemble a T = 16 structure using only 1 equivalent bonding interaction. Noteworthy, in principle, any triangulation number capsid can be assembled with just 1 equivalent interaction as long as the template size permits. We estimate this strategy has the potential to increase the yield of origami capsids by a million fold over current methods.