Nanotechnology Now

Our NanoNews Digest Sponsors
Heifer International

Wikipedia Affiliate Button

Home > Press > Two-lock box delivers cancer therapy: Rice University researchers find new possibilities for benign, ‘tunable’ virus

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
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

Abstract:
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.

Two-lock box delivers cancer therapy: Rice University researchers find new possibilities for benign, ‘tunable’ virus

Houston, TX | Posted on May 6th, 2014

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.
- See more at: http://news.rice.edu/2014/05/06/two-lock-box-delivers-cancer-therapy/#sthash.KTzEuHp2.dpuf

####

About Rice University
Located on a 300-acre forested campus in Houston, Rice University is consistently ranked among the nation’s top 20 universities by U.S. News & World Report. Rice has highly respected schools of Architecture, Business, Continuing Studies, Engineering, Humanities, Music, Natural Sciences and Social Sciences and is home to the Baker Institute for Public Policy. With 3,920 undergraduates and 2,567 graduate students, Rice’s undergraduate student-to-faculty ratio is 6.3-to-1. Its residential college system builds close-knit communities and lifelong friendships, just one reason why Rice has been ranked No. 1 for best quality of life multiple times by the Princeton Review and No. 2 for “best value” among private universities by Kiplinger’s Personal Finance.

Follow Rice News and Media Relations via Twitter @RiceUNews

For more information, please click here

Contacts:
David Ruth
713-348-6327


Mike Williams
713-348-6728

Copyright © Rice University

If you have a comment, please Contact us.

Issuers of news releases, not 7th Wave, Inc. or Nanotechnology Now, are solely responsible for the accuracy of the content.

Bookmark:
Delicious Digg Newsvine Google Yahoo Reddit Magnoliacom Furl Facebook

Related Links

Read the abstract at:

Laboratory for Nanotherapeutics Research (Suh):

Rice Department of Bioengineering:

Related News Press

News and information

New method to reduce uranium concentration in contaminated water March 18th, 2019

Review of the recent advances of 2D nanomaterials in Lit-ion batteries March 15th, 2019

Converting biomass by applying mechanical force Nanoscientists discover new mechanism to cleave cellulose effectively and in an environmentally friendly way March 15th, 2019

Exotic “second sound” phenomenon observed in pencil lead: At relatively balmy temperatures, heat behaves like sound when moving through graphite, study reports March 15th, 2019

Govt.-Legislation/Regulation/Funding/Policy

Exotic “second sound” phenomenon observed in pencil lead: At relatively balmy temperatures, heat behaves like sound when moving through graphite, study reports March 15th, 2019

Researchers reverse the flow of time on IBM's quantum computer March 14th, 2019

When semiconductors stick together, materials go quantum: A new study led by Berkeley Lab reveals how aligned layers of atomically thin semiconductors can yield an exotic new quantum material March 12th, 2019

Arrowhead Pharmaceuticals Begins Dosing in Phase 1 Study of ARO-APOC3 for Treatment of Hypertriglyceridemia March 11th, 2019

Nanomedicine

Arrowhead Pharmaceuticals Begins Dosing in Phase 1 Study of ARO-APOC3 for Treatment of Hypertriglyceridemia March 11th, 2019

New optical imaging system could be deployed to find tiny tumors: Near-infrared technology pinpoints fluorescent probes deep within living tissue; may be used to detect cancer earlier March 8th, 2019

Computer-designed vaccine elicits potent antibodies against RSV: The nanoparticle platform for this respiratory syncytial virus study will be applied to vaccine research on flu, HIV, and more; Seattle startup Icosavax will advance related clinical trials March 8th, 2019

CEA-Leti Breakthrough Opens Path to New Vaccine for HIV: Lipidots Platform Strengthens Immune Response to Protein That Is Key to HIV Vaccine; Results Presented in Nature Publishing Group’s npj Vaccines February 27th, 2019

Discoveries

New method to reduce uranium concentration in contaminated water March 18th, 2019

Review of the recent advances of 2D nanomaterials in Lit-ion batteries March 15th, 2019

Converting biomass by applying mechanical force Nanoscientists discover new mechanism to cleave cellulose effectively and in an environmentally friendly way March 15th, 2019

Quantum sensing method measures minuscule magnetic fields: MIT researchers find a new way to make nanoscale measurements of fields in more than one dimension March 15th, 2019

Announcements

New method to reduce uranium concentration in contaminated water March 18th, 2019

Review of the recent advances of 2D nanomaterials in Lit-ion batteries March 15th, 2019

Converting biomass by applying mechanical force Nanoscientists discover new mechanism to cleave cellulose effectively and in an environmentally friendly way March 15th, 2019

Exotic “second sound” phenomenon observed in pencil lead: At relatively balmy temperatures, heat behaves like sound when moving through graphite, study reports March 15th, 2019

Interviews/Book Reviews/Essays/Reports/Podcasts/Journals/White papers

New method to reduce uranium concentration in contaminated water March 18th, 2019

Review of the recent advances of 2D nanomaterials in Lit-ion batteries March 15th, 2019

Converting biomass by applying mechanical force Nanoscientists discover new mechanism to cleave cellulose effectively and in an environmentally friendly way March 15th, 2019

Quantum sensing method measures minuscule magnetic fields: MIT researchers find a new way to make nanoscale measurements of fields in more than one dimension March 15th, 2019

Nanobiotechnology

Arrowhead Pharmaceuticals Begins Dosing in Phase 1 Study of ARO-APOC3 for Treatment of Hypertriglyceridemia March 11th, 2019

Computer-designed vaccine elicits potent antibodies against RSV: The nanoparticle platform for this respiratory syncytial virus study will be applied to vaccine research on flu, HIV, and more; Seattle startup Icosavax will advance related clinical trials March 8th, 2019

Nanotechnology Gives Mice Night Vision—Are Humans Next? March 2nd, 2019

CEA-Leti Breakthrough Opens Path to New Vaccine for HIV: Lipidots Platform Strengthens Immune Response to Protein That Is Key to HIV Vaccine; Results Presented in Nature Publishing Group’s npj Vaccines February 27th, 2019

NanoNews-Digest
The latest news from around the world, FREE



  Premium Products
NanoNews-Custom
Only the news you want to read!
 Learn More
NanoStrategies
Full-service, expert consulting
 Learn More











ASP
Nanotechnology Now Featured Books




NNN

The Hunger Project