Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
PZ HTL SA
GLOBETECH PUBLISHING LLC

Nanodelivery System Securely Targets Cancer cells

By BiotechDaily International staff writers
Posted on 20 May 2014
Image 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 (Photo courtesy of Junghae Suh/Rice University).
Image 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 (Photo courtesy of Junghae Suh/Rice University).
Scientists have devised a tunable virus that works similar to a safe deposit box. It takes two keys to open it and release its therapeutic payload.

The Rice University (Houston, TX, USA) laboratory of bioengineer Dr. 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 specific proteases are elevated at tumor sites, the viruses can be designed to target and destroy the cancer cells.

The research was published online May 5, 2014, in the American Chemical Society (ACS) journal ACS Nano. AAVs are comparatively benign and have been intensely studied as delivery vehicles for gene therapies. Researchers frequently try to target AAVs to cellular receptors that may be somewhat overexpressed on diseased cells.

The Rice lab takes a different tactic. “We were looking for other types of biomarkers beyond cellular receptors present at disease sites,” Dr. 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.”

Dr. Suh’s lab genetically inserts peptides into the self-assembling AAVs to lock the capsids, the hard shells that protect genes positioned within. The target proteases spot the peptides “and chew off the locks,” effectively unlocking the virus and allowing it to attach 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.”

Molecular-imaging techniques in the future 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,” Dr. Suh said.

Dr. Suh reported that 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 neurologic diseases, such as stroke, Parkinson’s and Alzheimer’s diseases, and heart diseases, including myocardial infarction and congestive heart failure.

The eventual outcome 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,” Dr. Suh stated. “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.”

Related Links:

Rice University



SLAS - Society for Laboratory Automation and Screening
BIOSIGMA S.R.L.
RANDOX LABORATORIES
comments powered by Disqus

Channels

Genomics/Proteomics

view channel
Image: A 3-dimensional picture reveals how the antibodies in the experimental drug Zmapp bind to Ebola virus (Photo courtesy of the Scripps Research Institute).

Electron Microscope Imaging Shows How Experimental Anti-Ebola Drug Works

Electron microscope imaging has revealed how the experimental drug ZMapp binds to the Ebolavirus and provides insights into how the drug prevents growth of the pathogen. ZMapp, which was developed by... Read more

Drug Discovery

view channel

Omega 3 Found to Improve Behavior in Children with ADHD

Supplements of the fatty acids omega 3 and 6 can help children and adolescents who have a specific kind of have attention deficit hyperactivity disorder (ADHD). Moreover, these findings indicate that a customized cognitive training program can improve problem behavior in children with ADHD. Statistics show that 3%–6%... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Business

view channel

Two Industry Partnerships Initiated to Fuel Neuroscience Research

Faster, more complex neural research is now attainable by combining technology from two research companies. Blackrock Microsystems, LLC (Salt Lake City, UT, USA), a developer of neuroscience research equipment, announced partnerships with two neuroscience research firms—PhenoSys, GmbH (Berlin, Germany) and NAN Instruments, Ltd.... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.