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 Genetic Regulation of the Thymus Function Identified
23.08.2016 | Universität Basel

nachricht Sun protection for plants - Plant substances can protect plants against harmful UV radiation
22.08.2016 | Max-Planck-Institut für Molekulare Pflanzenphysiologie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Streamlining accelerated computing for industry

PyFR code combines high accuracy with flexibility to resolve unsteady turbulence problems

Scientists and engineers striving to create the next machine-age marvel--whether it be a more aerodynamic rocket, a faster race car, or a higher-efficiency jet...

Im Focus: X-ray optics on a chip

Waveguides are widely used for filtering, confining, guiding, coupling or splitting beams of visible light. However, creating waveguides that could do the same for X-rays has posed tremendous challenges in fabrication, so they are still only in an early stage of development.

In the latest issue of Acta Crystallographica Section A: Foundations and Advances , Sarah Hoffmann-Urlaub and Tim Salditt report the fabrication and testing of...

Im Focus: Piggyback battery for microchips: TU Graz researchers develop new battery concept

Electrochemists at TU Graz have managed to use monocrystalline semiconductor silicon as an active storage electrode in lithium batteries. This enables an integrated power supply to be made for microchips with a rechargeable battery.

Small electrical gadgets, such as mobile phones, tablets or notebooks, are indispensable accompaniments of everyday life. Integrated circuits in the interiors...

Im Focus: UCI physicists confirm possible discovery of fifth force of nature

Light particle could be key to understanding dark matter in universe

Recent findings indicating the possible discovery of a previously unknown subatomic particle may be evidence of a fifth fundamental force of nature, according...

Im Focus: Wi-fi from lasers

White light from lasers demonstrates data speeds of up to 2 GB/s

A nanocrystalline material that rapidly makes white light out of blue light has been developed by KAUST researchers.

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

New Ideas for the Shipping Industry

24.08.2016 | Event News

A week of excellence: 22 of the world’s best computer scientists and mathematicians in Heidelberg

12.08.2016 | Event News

Towards the connected, automated and electrified automobiles: AMAA conference in Brussels

02.08.2016 | Event News

 
Latest News

New Ideas for the Shipping Industry

24.08.2016 | Event News

Lehigh engineer discovers a high-speed nano-avalanche

24.08.2016 | Physics and Astronomy

Streamlining accelerated computing for industry

24.08.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>