Sneaky Virus
Packs Healthy Punch

Drs. Stefan Franzen and Steve Lommel are running a smuggling operation in their labs on Centennial Campus. They are sneaking a cache of disease-fighting weapons through the body’s defenses and hope to destroy or reprogram targeted cells. Their secret weapon? A modified 38-nanometer plant virus.

“This system has the potential to fight
a lot of diseases.”

The red clover necrotic mosaic virus infects fruit trees and clover in temperate regions and is one of the few viruses that can survive outside a host organism. Lommel, a professor of plant pathology and genetics in the College of Agriculture and Life Sciences, was studying how the virus assembles itself, looking for possible clues to battling HIV, when he discovered a tiny cavity inside. He thought the 17-nanometer “cargo hold” would be perfect for packaging things for transport.

Meanwhile, Franzen, a chemistry professor in the College of Physical and Mathematical Sciences, was trying to use gold nanoparticles for more targeted delivery of cancer therapies. He attached the drugs to the gold, along with peptides that would link up only with the tumor cells. But he thought hiding the drugs inside something else would work better than exposing them to the body’s defense mechanisms. Both researchers happened to be working in Poland a few years ago when they swapped notes about their efforts and began to collaborate.

The clover virus is a shell of 180 copies of a single protein built around two RNA strands. Under appropriate conditions, dozens of pores open up on its surface, Lommel says. Therapeutic agents can then be pumped into the internal cavity before the pores are closed again. Franzen has attached adenovirus peptides—widely used in gene therapy—to the virus to show that various cell types will take in the Trojan horse-like drug delivery system (see cover illustration). “Plant viruses don’t work like human viruses, so we’re not concerned that our virus has any interest in going after any cells in the body,” Lommel says. “It’s really an elegant drug delivery system.”

Therapeutic agents can be pumped into the internal cavity of a genetically modified plant virus to create a Trojan horse-like drug delivery system.

Lommel and Franzen are now trying to show that the system can target certain cancer cells, and they’re also working with scientists at UNC-Chapel Hill, Duke and in Poland to place RNA inside the virus shell to attack genetic diseases like sickle-cell anemia. “RNA is the normal cargo of the virus, so we might be able to reprogram cells by using it to release very short strands of RNA,” Franzen says.“This system has the potential to fight a lot of diseases.”

http://chsfpc5.chem.ncsu.edu/~franzen/sf/nanobio/index.htm

 

Drs. Stefan Franzen, left, and Steve Lommel with a model of the modified plant virus they hope to use as a drug delivery system.

a b c

Resolved by cryo-electron microscopy, the structure of red clover necrotic mosaic virus reveals details of the icosahedral capsid (a). Cross section (b) reveals the presence of an ordered inner core (shaded blue). Structural analysis of the inner core in isolation (c) reveals that it has dodecahedral symmetry and is comprised of an RNA/protein complex.