Navigation Links
Novel nanotechnology collaboration leads to breakthrough in cancer research
Date:9/1/2010

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.


'/>"/>

Contact: Mike Rodewald
mrodewald@cnsi.ucla.edu
310-267-5883
University of California - Los Angeles
Source:Eurekalert

Related medicine news :

1. Novel autoantibodies identified in patients with necrotizing myopathy
2. Novel role: EZH2 boosts creation of ovarian cancer blood vessels
3. FSU study takes novel approach to understanding pituitary function
4. OU researcher developing novel therapy for Alzheimers disease
5. Vitamin B3 as a novel approach to treat fungal infections
6. Announcing: Intrinsic Imaging : Radiology Experts Launch Novel Medical Imaging CRO for Clinical Trials
7. Novel approaches to R&D in Africa needed
8. Novel radiotracer shines new light on the brains of Alzheimers disease patients
9. Team led by LA BioMed scientist develops novel approach to study neurological disorders
10. Novel paclitaxel formulation encouraging for treating advanced lung cancer
11. Novel Drug Combats Advanced Melanoma
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/24/2016)... , ... June 24, 2016 , ... Those who have ... these feelings, many turn to unhealthy avenues, such as drug or alcohol abuse, as ... Michigan, has released tools for healthy coping following a traumatic event. , Trauma sufferers ...
(Date:6/24/2016)... ... ... in a crisis. Her son James, eight, was out of control. Prone to extreme mood ... something upset him, he couldn’t control his emotions,” remembers Marcy. “If there was a ... children and say he was going to kill them. If we were driving on ...
(Date:6/24/2016)... , ... June 24, 2016 , ... Global law firm ... 2016 Legal Elite. The attorneys chosen by their peers for this recognition are considered ... Seven Greenberg Traurig Shareholders received special honors as members of this year’s Legal Elite ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... Comfort Keepers® ... American Cancer Society and the Road To Recovery® program to drive cancer patients to ... and other adults to ensure the highest quality of life and ongoing independence. ...
(Date:6/24/2016)... ... June 24, 2016 , ... People across the U.S. are sharpening their pencils ... an essay contest in which patients and their families pay tribute to a genetic ... 2016 National Society of Genetic Counselors (NSGC) Annual Education Conference (AEC) this September. ...
Breaking Medicine News(10 mins):
(Date:6/24/2016)... , June 24, 2016   Bay ... Rehabilitation Network,s Dean Center for Tick Borne ... Medicine and Rehabilitation, MIT Hacking Medicine, University of ... Innovation, today announced the five finalists of ... Lyme disease.  More than 100 scientists, clinicians, researchers, ...
(Date:6/24/2016)... June 24, 2016 Research ... "Structural Electronics 2015-2025: Applications, Technologies, Forecasts" ... In-Mold Electronics, Smart Skin, Structural Health ... Structural electronics involves electronic and/or electrical ... structures, replacing dumb structures such as vehicle bodies ...
(Date:6/24/2016)... , June 24, 2016 Dehaier Medical ... the "Company"), which develops, markets and sells medical devices ... , signed a strategic cooperation agreement with Hongyuan ... "Hongyuan Supply Chain") on June 20, 2016, to develop ... the strategic cooperation agreement, Dehaier will leverage Hongyuan Supply ...
Breaking Medicine Technology: