Team modifies nanoscale virus to deliver peptide drugs to cells, tissues

By chipping away at a viral protein, Rice University scientists have discovered a path toward virus-like, nanoscale devices that may be able to deliver drugs to cells.

The protein is one of three that make up the protective shell, called the capsid, of natural adeno-associated viruses (AAV). By making progressively smaller versions of the protein, the researchers made capsids with unique abilities and learned a great deal about AAV’s mechanisms.

The research appears in the American Chemical Society journal ACS Nano.

Rice bioengineer Junghae Suh studies the manipulation of nondisease-causing AAVs to deliver helpful cargoes like chemotherapy drugs. Her research has led to the development of viruses that can be triggered by light or by extracellular proteases associated with certain diseases.

AAVs are small—about 25 nanometers—and contain a single strand of DNA inside tough capsids that consist of a mosaic of proteins known as VP1, VP2 and VP3. AAVs have been used to deliver gene-therapy payloads, but nobody has figured out how AAV capsids physically reconfigure themselves when triggered by external stimuli, Suh said. That was the starting point for her lab.

“This virus has intrinsic peptide (small protein) domains hidden inside the capsid,” she said. “When the virus infects a cell, it senses the low pH and other endosomal factors, and these peptide domains pop out onto the surface of the virus capsid.

“This conformational change, which we termed an ‘activatable peptide display,’ is important for the virus because the externalized domains break down the endosomal membrane and allow the virus to escape into the cytoplasm,” Suh said. “In addition, nuclear localization sequences in those domains allow the virus to transit into the nucleus. We believed we could replace that functionality with something else.”

Read more at phys.org

Image Credit:  Jeff Fitlow/Rice University

 

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