Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Two-lock box delivers cancer therapy

07.05.2014

Rice University researchers find new possibilities for benign, ‘tunable’ virus

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.


An adeno-associated virus capsid (blue) modified by peptides (red) inserted to lock the virus is the result of research at Rice University into a new way to target cancerous and other diseased cells. The peptides are keyed to proteases overexpressed at the site of diseased tissues; they unlock the capsid and allow it to deliver its therapeutic cargo. (Credit: Junghae Suh/Rice University)

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. “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.

“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.” In the future, molecular-imaging approaches will be used to detect both the identity and concentration of elevated proteases.

“With that information, we would be able to pick a virus device from our panel of engineered variants that has the right properties to target that disease site. That’s where we want to go,” she said. Suh said elevated proteases are found around many diseased tissues. She suggested these protease-activatable viruses may be useful for the treatment of not only cancers but also neurological diseases, such as stroke, Parkinson’s and Alzheimer’s diseases, and heart diseases, including myocardial infarction and congestive heart failure. The ultimate vision of this technology is to design viruses that can carry out a combination of steps for targeting.

“To increase the specificity of virus unlocking, you can imagine creating viruses that require many more keys to open,” she said. “For example, you may need both proteases A and B as well as a cellular receptor to unlock the virus. The work reported here is a good first step toward this goal.”

Co-authors are Rice alumni Justin Judd and Abhinav Tiwari; graduate students Michelle Ho, Eric Gomez and Christopher Dempsey; Oleg Igoshin, an associate professor of bioengineering; and Jonathan Silberg, an associate professor of biochemistry and cell biology, all at Rice; and Kim Van Vliet, an assistant research scientist, and Mavis Agbandje-McKenna, a professor, both at the University of Florida. Suh is an assistant professor of bioengineering. The National Science Foundation, the National Institutes of Health, the American Heart Association and the Cancer Prevention and Research Institute of Texas supported the research.

David Ruth | Eurek Alert!
Further information:
http://news.rice.edu/2014/05/06/two-lock-box-delivers-cancer-therapy/

Further reports about: Heart diseases effects enzymes genes myocardial peptides proteases stroke targeting therapy viruses

More articles from Life Sciences:

nachricht How to become a T follicular helper cell
31.07.2015 | La Jolla Institute for Allergy and Immunology

nachricht Heating and cooling with light leads to ultrafast DNA diagnostics
31.07.2015 | University of California - Berkeley

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Quantum Matter Stuck in Unrest

Using ultracold atoms trapped in light crystals, scientists from the MPQ, LMU, and the Weizmann Institute observe a novel state of matter that never thermalizes.

What happens if one mixes cold and hot water? After some initial dynamics, one is left with lukewarm water—the system has thermalized to a new thermal...

Im Focus: On the crest of the wave: Electronics on a time scale shorter than a cycle of light

Physicists from Regensburg and Marburg, Germany have succeeded in taking a slow-motion movie of speeding electrons in a solid driven by a strong light wave. In the process, they have unraveled a novel quantum phenomenon, which will be reported in the forthcoming edition of Nature.

The advent of ever faster electronics featuring clock rates up to the multiple-gigahertz range has revolutionized our day-to-day life. Researchers and...

Im Focus: Superfast fluorescence sets new speed record

Plasmonic device has speed and efficiency to serve optical computers

Researchers have developed an ultrafast light-emitting device that can flip on and off 90 billion times a second and could form the basis of optical computing.

Im Focus: Unlocking the rice immune system

Joint BioEnergy Institute study identifies bacterial protein that is key to protecting rice against bacterial blight

A bacterial signal that when recognized by rice plants enables the plants to resist a devastating blight disease has been identified by a multi-national team...

Im Focus: Smarter window materials can control light and energy

Researchers in the Cockrell School of Engineering at The University of Texas at Austin are one step closer to delivering smart windows with a new level of energy efficiency, engineering materials that allow windows to reveal light without transferring heat and, conversely, to block light while allowing heat transmission, as described in two new research papers.

By allowing indoor occupants to more precisely control the energy and sunlight passing through a window, the new materials could significantly reduce costs for...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

3rd Euro Bio-inspired - International Conference and Exhibition on Bio-inspired Materials

23.07.2015 | Event News

Clash of Realities – International Conference on the Art, Technology and Theory of Digital Games

10.07.2015 | Event News

World Conference on Regenerative Medicine in Leipzig: Last chance to submit abstracts until 2 July

25.06.2015 | Event News

 
Latest News

Tool making and additive technology exhibition: Fraunhofer IPT at Formnext

31.07.2015 | Trade Fair News

First Siemens-built Thameslink train arrives in London

31.07.2015 | Transportation and Logistics

California 'rain debt' equal to average full year of precipitation

31.07.2015 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>