Single-building-block design yields versatile quasisymmetric protein nanocages

Researchers demonstrate de novo design of large, quasisymmetric protein cages built from a single building block. By leveraging spontaneous symmetry breaking, a parametric cage-design framework, and RoseTTAFold diffusion modelling (with ProteinMPNN for sequence design), they generate 3 ≤ T ≤ 36 cages containing 180–2,160 subunits and diameters from 68 to 220 nm. Cryo-EM confirms the structures and shows symmetry breaking across non-equivalent subunit positions, expanding the design space for one-component cages with potential for delivering biologics at large internal volumes.