Figure 2.

Designable features of nanoparticle scaffolds. Two main considerations when designing protein nanoparticle delivery systems are scaffold source and scaffold modifications. (A–C) Protein nanoparticle geometries commonly used for delivery applications have icosahedral, octahedral, tetrahedral, or dihedral symmetry.^18,19,71 Notably, the octahedral nanoparticle in (B) is composed of eight identical trimer subunits, which are colored differently to help visually distinguish individual subunits in the context of the global structure. (D–F) Additional functional elements are designed into the nanoparticle through subunit interface, interior, and exterior modifications.²⁵ (D) Interfaces between the trimer subunits (slate) and pentamer subunits (gray) were computationally designed. (E) Interior residues were mutated to hold a net positive charge, leading to electrostatic association of mRNA. (F) Additional protein domains can be displayed on the surface of existing nanoparticles. A, D: Reprinted with permission.(18) B: Reprinted with permission.(19) C: Reprinted with permission.(71)