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Two-lock box delivers cancer therapy
Date:5/6/2014

Rice University scientists have designed a tunable virus that works like a safe deposit box. It takes two keys to open it and release its therapeutic cargo.

The Rice lab of bioengineer Junghae Suh has developed an adeno-associated virus (AAV) that unlocks only in the presence of two selected proteases, enzymes that cut up other proteins for disposal. Because certain proteases are elevated at tumor sites, the viruses can be designed to target and destroy the cancer cells.

The work appears online this week in the American Chemical Society journal ACS Nano.

AAVs are fairly benign and have become the object of intense study as delivery vehicles for gene therapies. Researchers often try to target AAVs to cellular receptors that may be slightly overexpressed on diseased cells.

The Rice lab takes a different approach. "We were looking for other types of biomarkers beyond cellular receptors present at disease sites," Suh said. "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."

Suh's lab genetically inserts peptides into the self-assembling AAVs to lock the capsids, the hard shells that protect genes contained within. The target proteases recognize the peptides "and chew off the locks," effectively unlocking the virus and allowing it to bind to the diseased cells.

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Contact: David Ruth
david@rice.edu
713-348-6327
Rice University
Source:Eurekalert  

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