For this work, Frank Sainsbury and colleagues copied the core protein shell of the Bluetongue virus, a pathogen that affects ruminant animals. Previous research has shown that the capsid is stable, has a large cavity for small molecules or proteins to pack into, and is easy to produce with high purity. The researchers wanted to try making the virus-shell nanoparticles using plants. This is an increasingly popular approach to producing pharmaceuticals as it minimizes possible contamination by human pathogens, which plants don’t carry. But first they needed to understand the structure of the shells.
Using single particle cryo-electron microscopy, the team showed for the first time that the recombinant shell nanoparticles produced by plants were different from the natural virus capsid. With the nanoparticles’ detailed structure in hand, the researchers then genetically and chemically engineered them to their specifications, and loaded proteins and small molecules inside the shells. Lab testing showed that the plant-made virus particles, which naturally bind to receptors on cancer cells, were taken in by human breast cancer cells. The findings suggest the nanoparticles can potentially be used for the targeted delivery of drugs.