Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Novel nanotechnology collaboration leads to breakthrough in cancer research

01.09.2010
Researchers clear hurdle on path toward gene-therapy treatment for disease
One of the most difficult aspects of working at the nanoscale is actually seeing the object being worked on. Biological structures like viruses, which are smaller than the wavelength of light, are invisible to standard optical microscopes and difficult to capture in their native form with other imaging techniques.

A multidisciplinary research group at UCLA has now teamed up to not only visualize a virus but to use the results to adapt the virus so that it can deliver medication instead of disease.

In a paper published last week in the journal Science, Hongrong Liu, a UCLA postdoctoral researcher in microbiology, immunology and molecular genetics, and colleagues reveal an atomically accurate structure of the adenovirus that shows the interactions among its protein networks. The work provides critical structural information for researchers around the world attempting to modify the adenovirus for use in vaccine and gene-therapy treatments for cancer.

To modify a virus for gene therapy, researchers remove its disease-causing DNA, replace it with medications and use the virus shell, which has been optimized by millions of years of evolution, as a delivery vehicle.

Lily Wu, a UCLA professor of molecular and medical pharmacology and co-lead author of the study, and her group have been attempting to manipulate the adenovirus for use in gene therapy, but the lack of information about receptors on the virus's surface had hampered their quest.

"We are engineering viruses to deliver gene therapy for prostate and breast cancers, but previous microscopy techniques were unable to visualize the adapted viruses," Wu said. "This was like trying to a piece together the components of a car in the dark, where the only way to see if you did it correctly was to try and turn the car on."

To better visualize the virus, Wu sought assistance from Hong Zhou, a UCLA professor of microbiology, immunology and molecular genetics and the study's other lead author. Zhou uses cryo-electron microscopy (cryoEM) to produce atomically accurate three-dimensional models of biological samples such as viruses.

Wu, who is also a researcher at the California NanoSystems Institute (CNSI) at UCLA, learned of Zhou's work after he was jointly recruited to UCLA from the University of Texas Medical School at Houston by the UCLA Department of Microbiology, Immunology and Molecular Genetics and UCLA's CNSI.

About a year ago, once the transfer of Zhou's lab was complete, Sok Boon Koh, one of Wu's students, sought out Zhou's group for their expertise and initiated the collaboration.

"This project exemplifies my excitement about being part of an institute as innovative as CNSI," Zhou said. "Not only am I able to work with state-of-the-art equipment, but because CNSI is the hub for nanotechnology research and commercialization at UCLA, I have the opportunity to collaborate with colleagues across many disciplines."

Working in the Electron Imaging Center for Nanomachines at the CNSI, a lab run by Zhou, the researchers used cryoEM to create a 3-D reconstruction of the human adenovirus from 31,815 individual particle images.

"Because the reconstruction reveals details up to a resolution of 3.6 angstroms, we are able to build an atomic model of the entire virus, showing precisely how the viral proteins all fit together and interact," Zhou said. An angstrom is the distance between the two hydrogen atoms in a water molecule, and the entire adenovirus is about 920 angstroms in diameter.

Armed with this new understanding, Wu and her group are now moving forward with their engineered versions of adenovirus to use for gene therapy treatment of cancer.

"This breakthrough is a great leap forward, but there are still many obstacles to overcome," Wu said. "If our work is successful, this therapy could be used to treat most forms of cancer, but our initial efforts have focused on prostate and breast cancers because those are the two most common forms of cancer in men and women, respectively."

The group is working with the adenovirus because previous research has established it as a good candidate for gene therapy due to its efficiency in delivering genetic materials inside the body. The virus shell is also a safe delivery vehicle; tests have shown that the shell does not cause cancer, a problem encountered with some other virus shells. The adenovirus is relatively non-pathogenic naturally, causing only temporary respiratory illness in 5 to 10 percent of people.

CryoEM enables such a high-resolution reconstruction of biological structures because samples, in water, are imaged directly. In contrast, with X-ray crystallography (the conventional technique for atomic resolution models of biological structures), researchers grow crystal structures replicating the sample and then use diffraction to solve the crystal structure. This technique is limited because it is difficult to grow crystals for all proteins, samples for x-ray crystallography need to be very pure and uniform, and crystals of large complexes may not diffract to high resolution. These limitations resulted in critical areas of the adenovirus surface being unresolved using x-ray crystallography.

The study was funded by the National Cancer Institute and the U.S. Department of Defense.

The California NanoSystems Institute at UCLA is an integrated research center operating jointly at UCLA and UC Santa Barbara whose mission is to foster interdisciplinary collaborations for discoveries in nanosystems and nanotechnology; train the next generation of scientists, educators and technology leaders; and facilitate partnerships with industry, fueling economic development and the social well-being of California, the United States and the world. The CNSI was established in 2000 with $100 million from the state of California and an additional $250 million in federal research grants and industry funding. At the institute, scientists in the areas of biology, chemistry, biochemistry, physics, mathematics, computational science and engineering are measuring, modifying and manipulating the building blocks of our world — atoms and molecules. These scientists benefit from an integrated laboratory culture enabling them to conduct dynamic research at the nanoscale, leading to significant breakthroughs in the areas of health, energy, the environment and information technology.

For more news, visit the UCLA Newsroom and follow us on Twitter.

Mike Rodewald | EurekAlert!
Further information:
http://www.ucla.edu

More articles from Interdisciplinary Research:

nachricht Many muons: Imaging the underground with help from the cosmos
19.12.2016 | DOE/Pacific Northwest National Laboratory

nachricht Lego-like wall produces acoustic holograms
17.10.2016 | Duke University

All articles from Interdisciplinary Research >>>

The most recent press releases about innovation >>>

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

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>