Featured Research

from universities, journals, and other organizations

Two-lock box delivers cancer therapy: Nano-delivery system targets cancer cells

Date:
May 6, 2014
Source:
Rice University
Summary:
A tunable virus that works like a safe deposit box has been developed by scientists. It takes two keys to open it and release its therapy for cancer and other diseases. The adeno-associated virus (AAV) developed by bioengineers 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.

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

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.

Related Articles


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."


Story Source:

The above story is based on materials provided by Rice University. The original article was written by Mike Williams. Note: Materials may be edited for content and length.


Journal Reference:

  1. Justin Judd, Michelle L. Ho, Abhinav Tiwari, Eric J. Gomez, Christopher Dempsey, Kim Van Vliet, Oleg A. Igoshin, Jonathan J. Silberg, Mavis Agbandje-McKenna, Junghae Suh. Tunable Protease-Activatable Virus Nanonodes. ACS Nano, 2014; 140505143944005 DOI: 10.1021/nn500550q

Cite This Page:

Rice University. "Two-lock box delivers cancer therapy: Nano-delivery system targets cancer cells." ScienceDaily. ScienceDaily, 6 May 2014. <www.sciencedaily.com/releases/2014/05/140506130437.htm>.
Rice University. (2014, May 6). Two-lock box delivers cancer therapy: Nano-delivery system targets cancer cells. ScienceDaily. Retrieved March 31, 2015 from www.sciencedaily.com/releases/2014/05/140506130437.htm
Rice University. "Two-lock box delivers cancer therapy: Nano-delivery system targets cancer cells." ScienceDaily. www.sciencedaily.com/releases/2014/05/140506130437.htm (accessed March 31, 2015).

Share This


More From ScienceDaily



More Health & Medicine News

Tuesday, March 31, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Soda, Salt and Sugar: The Next Generation of Taxes

Soda, Salt and Sugar: The Next Generation of Taxes

Washington Post (Mar. 30, 2015) — Denisa Livingston, a health advocate for the Dinι Community Advocacy Alliance, and the Post&apos;s Abby Phillip discuss efforts around the country to make unhealthy food choices hurt your wallet as much as your waistline. Video provided by Washington Post
Powered by NewsLook.com
UnitedHealth Buys Catamaran

UnitedHealth Buys Catamaran

Reuters - Business Video Online (Mar. 30, 2015) — The $12.8 billion merger will combine the U.S.&apos; third and fourth largest pharmacy benefit managers. Analysts say smaller PBMs could also merge. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
S. Leone in New Anti-Ebola Lockdown

S. Leone in New Anti-Ebola Lockdown

AFP (Mar. 28, 2015) — Sierra Leone imposed a three-day nationwide lockdown Friday for the second time in six months in a bid to prevent a resurgence of the deadly Ebola virus. Duration: 01:17 Video provided by AFP
Powered by NewsLook.com
These Popular Antibiotics Can Cause Permanent Nerve Damage

These Popular Antibiotics Can Cause Permanent Nerve Damage

Newsy (Mar. 27, 2015) — A popular class of antibiotic can leave patients in severe pain and even result in permanent nerve damage. Video provided by Newsy
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins