A team at Stanford University, led by Professor James Swartz, recently reported a major advancement in nano-particle drug research. This research group used the Hepatitis B virus and re-engineered its capsid to become a virus-like particle (VLP). Many other researchers have tried to create VLPs, and more specifically tried to reprogram the HepB virus to act as a drug delivery capsule, but it had proven extremely difficult to do so experimentally. Because of past failures to repurpose the virus, funding was hard to obtain to support this research project. In the end, however, Dr. Swartz was able to finish the study after four years.
In order to succeed where others had failed, the team at Stanford looked into the DNA of the virus. The group altered the genetic code itself so that the capsid would rearrange to hide itself from the body’s immune system. Furthermore, the team modified the capsid in many ways including artificial covalent disulfide bridges to improve nanoparticle stability, removing the surface charge, and adding a rare spike region of proteins on the shell structure. They made all these modifications without disrupting the internal proteins of the HepB virus to self-assemble into a spiky VLP.
Overall, their work will now allow other groups to produce stabilized VLPs for applications in vaccines, delivery vehicles, and even imaging agents. The researchers hopes to further this technology by adding cancer tags so that once the nanoparticle reaches a cancer cell, it signals the body’s immune system to specifically target the tumor. Dr. Swartz currently has a patent on this technology and has licensed out some aspects of it to biotech companies.
Study in PNAS: Assessing sequence plasticity of a virus-like nanoparticle by evolution…
Press release: Stanford team re-engineers virus to deliver therapies to cells