Scientists use directed evolution to develop better viruslike capsules

Artificial viral capsids that hold their own genomic material could aid drug delivery


Schematic shows how bacteria produce synthetic capsids from introduced genes.
To produce synthetic capsids, bacteria transcribe two DNA genes (not shown) into one piece of mRNA (bicistronic) and translate the mRNA into proteins, which oligomerize to trimers and pentamers. The oligomers bind their encoding mRNA and self-assemble into capsids that can then be tested in mice.
Credit: Adapted from Nature

Viruses are pretty simple: They’re small DNA or RNA genomes enclosed in protein containers called capsids. Scientists have designed and engineered proteins that self-assemble into viruslike containers that hold cargoes such as drugs, vaccines, and biomolecules.

David Baker of the University of Washington and coworkers have now devised the first so-called nucleocapsids, artificial capsids that enclose their own RNA genomes. The development opens the door for researchers to use directed evolution, a repetitive protein mutation and screening technique, to optimize the properties of these protein containers for drug delivery applications (Nature 2017, DOI: 10.1038/nature25157).

In particular, the team optimized nucleocapsids to remain stable for long times and to protect their RNA cargoes from degradation while floating around in the bloodstreams of mice. The artificial nucleocapsids could be useful for delivering small molecules, biomolecules, or materials for therapeutic or nanomaterials applications. They could even provide housing for future synthetic lifeforms, the researchers say.  Rest