LAUSR

Directed Evolution Artificial nucleocapsid proteins, which could be analogous to those used by viruses to package their genomes, are a promising way to protect and deliver RNAs. Using an escalating challenge by nucleases, Tetter et al. evolved a protein that forms multimeric, spherical cages into a highly efficient capsid that selectively packages its own encoding RNA. Cryo–electron microscopy of the final design and intermediates revealed a stepwise expansion in size, enabled by destabilizing amino acid substitutions and a domain swap that results in a change of oligomerization interfaces for the base units of the cage. In addition to altering the protein, directed evolution resulted in changes to the encoding RNA structure that enabled efficient uptake versus other cellular RNAs. Science , abg2822, this issue p. [1220][1] [1]: /lookup/doi/10.1126/science.abg2822