Scientists Create Tunable Virus That Works Like a Safe Deposit Box
Scientists at Rice University have developed a tunable virus that works like a safe deposit box. At first it takes two keys to open it and then releases its therapeutic cargo.
The developed 'adeno-associated virus (AAV)' unlocks only in the presence of two selected proteases - enzymes that cut up other proteins for disposal.
The viruses can be designed to target and destroy the cancer cells as certain proteases are elevated at tumor sites.
"We were looking for other types of biomarkers beyond cellular receptors present at disease sites," said The Rice lab of bioengineer Junghae Suh, in the press release. "In breast cancer, for example, it's known the tumor cells oversecrete extracellular proteases, but perhaps more important are the infiltrating immune cells that migrate into the tumor microenvironment and start dumping out a whole bunch of proteases as well.
"So that's what we're going after to do targeted delivery. Our basic idea is to create viruses that, in the locked configuration, can't do anything. They're inert," she said. When programmed AAVs encounter the right protease keys at sites of disease, "these viruses unlock, bind to the cells and deliver payloads that will either kill the cells for cancer therapy or deliver genes that can fix them for other disease applications."
The research involves genetically inserting peptides into the self-assembling AAVs to lock the capsids - hard shells that protect genes contained within.
"If we were just looking for one protease, it might be at the cancer site, but it could also be somewhere else in your body where you have inflammation. This could lead to undesirable side effects," she said in the press release. "By requiring two different proteases - let's say protease A and protease B - to open the locked virus, we may achieve higher delivery specificity since the chance of having both proteases elevated at a site becomes smaller."
The work has been published in the American Chemical Society journal ACS Nano.