Overview of two-component icosahedral protein cages constructed through a computational design method. Icosahedral cages created by combining building blocks with different rotational symmetry were designed: I53–40 (a-c), I52–32 (d-f) and I32–28 (g-i). (a, d, g) show icosahedra outlined in gray dashed lines with three different combinations of symmetry axes (left). Models created by aligning pentameric, trimeric and dimeric proteins along target symmetry axes. Translational and rotational parameters are optimized by systematic screening. (b, e, h) Crystal structures of the designed cages. Views are shown along three-fold, two-fold and five-fold axes. (c, f, i) ns-TEM characterization of the designed cages (100 nm scale bar). Adapted with permission from Ref.391. Copyright 2016 AAAS.