Programmable self-assembly of DNA origami and proteins using symmetry guided principles

We provide a general and modular solution for building synthetic self-assembled nano structures based on programming DNA and proteins to fold into a few distinct monomers designed for assembly into large, but finite sized objects. We exploit symmetry in our design to minimize the number of unique monomers in a final structure. One successful example is icosahedral shells on the scale of 100 – 1000 nm, motivated by the 1962 Caspar and Klug theory of virus structure. The methods of DNA origami were employed to produce accurately designed building blocks. We explored strategies for controlling the assembly pathways, kinetics, and the yield by which subunits arrange themselves into icosahedral symmetry. We created multiple large virus-like capsids and validated the structures using cryo electron microscopy and studied the capsid assembly process experimentally and with a computational model to elucidate how the kinetics and yield of target structures depends on control parameters. Our capsid building blocks represent a near-ideal manifestation of patchy particles whose geometry and interactions can be designed with sub-nanometer and kBT precision, thus achieving a long sought after goal in soft matter physics. We extended our designs to include cylinders and surfaces with negative Gaussian curvature.  Now we are assessing whether the engineering principles we elucidated for DNA origami are applicable to de novo protein design, recently made possible with the introduction of AI tools, such as AlphaFold.