Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

’Stop leak’ solution found for toxicity problems in experimental gene therapy

09.09.2003


A Duke University research collaboration has identified a likely route for "leakage" of therapeutic gene-bearing viruses out of tumors in experimental anti-cancer gene therapy experiments in laboratory animals. The group also found this toxic leakage can be avoided by using a chemical extracted from common brown algae.



Their work was described in a 9:30 a.m. Sept. 8 presentation at the American Chemical Society’s national meeting in New York, as well as in a research paper accepted for publication in the journal Molecular Cancer Therapeutics.

Investigators from the biomedical engineering department at Duke’s Pratt School of Engineering and the radiation oncology department at the Duke Medical Center collaborated to trace why high concentrations of the protein produced by the therapeutic genes were present in the wrong places during animal experiments directed against tumors.


The experiments involved transplanting tumors into the legs of mice and then injecting those tumors with adenoviruses genetically altered to carry the cancer-fighting gene. About 24 hours after those adenoviruses infected the tumor cells, the virus-carried genes could then begin manufacturing a known anti-cancer protein called mouse interleukin-12 (IL-12).

When the researchers first tried the experiment using concentrations of IL-12 genes in the viruses they judged high enough to treat the cancer, "the animals died within 10 minutes," said Fan Yuan, a Duke associate professor of biomedical engineering, in an interview.

Exploring the reasons for the sudden deaths, the group used lower gene amounts that the animals could tolerate to trace what happened in their bodies during the extended infection and gene expression process.

They found that the virus preparations did not stay in the tumors as planned but also moved elsewhere in significant concentrations, principally to the liver.

The reason for that unanticipated migration was tumor blood vessel damage by the injection needle, Yuan said. After entering those vessels through the tiny wounds, viruses could quickly migrate through the entire interconnected bloodstream.

Identifying the problem, the Duke researchers also discovered an answer when they mixed the virus preparation with alginate, a major constituent of the cell walls of brown algae.

Injecting the combination of alginate and virus into the mouse tumors reduced by eight-fold the concentration of IL-12 in the animals’ livers compared to injecting the gene-bearing virus alone, the investigators found.

"The alginate solution is simple and straightforward," said Yuan, who added that this algae preparation is a nontoxic biocompatible polysaccharide used in tissue engineering.

The researchers suspect that the alginate solution’s high viscosity, about 1,000 times higher than water’s, may block most of the viruses from leaking out of the tumor tissue through injection wounds.

Such an action, Yuan acknowledged, would resemble how certain automotive products can stop leaks in radiators and power steering or oil circulation systems. "That’s the same analogy," he said. "It’s like Jello."

But that high viscosity also makes injecting the viruses into tumors more difficult. "You really have to push very hard," Yuan said.

So the researchers are now investigating whether other kinds of long-chained molecular polymers will block viral leaks as effectively as the alginate. With those, "you can use a very small force to push them through the needle," Yuan said.


###
Besides Yuan, others in group include Yong Wang, Yuan’s graduate student; Ava Krol, Yuan’s research associate; Chuan-Yuan Li, an associate research professor in radiation oncology; and Jim Kang Hu and Yong-Ping Li, research associates of Chuan-Yuan Li.

The work was supported by the National Science Foundation and National Institutes of Health.

Monte Basgall | EurekAlert!
Further information:
http://www.duke.edu/

More articles from Health and Medicine:

nachricht New leukemia treatment offers hope
23.09.2016 | King Abdullah University of Science and Technology

nachricht Alzheimer’s: Cellular Mechanism Provides Explanation Model for Declining Memory Performance
21.09.2016 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: OLED microdisplays in data glasses for improved human-machine interaction

The Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP has been developing various applications for OLED microdisplays based on organic semiconductors. By integrating the capabilities of an image sensor directly into the microdisplay, eye movements can be recorded by the smart glasses and utilized for guidance and control functions, as one example. The new design will be debuted at Augmented World Expo Europe (AWE) in Berlin at Booth B25, October 18th – 19th.

“Augmented-reality” and “wearables” have become terms we encounter almost daily. Both can make daily life a little simpler and provide valuable assistance for...

Im Focus: Artificial Intelligence Helps in the Discovery of New Materials

With the help of artificial intelligence, chemists from the University of Basel in Switzerland have computed the characteristics of about two million crystals made up of four chemical elements. The researchers were able to identify 90 previously unknown thermodynamically stable crystals that can be regarded as new materials. They report on their findings in the scientific journal Physical Review Letters.

Elpasolite is a glassy, transparent, shiny and soft mineral with a cubic crystal structure. First discovered in El Paso County (Colorado, USA), it can also be...

Im Focus: Complex hardmetal tools out of the 3D printer

For the first time, Fraunhofer IKTS shows additively manufactured hardmetal tools at WorldPM 2016 in Hamburg. Mechanical, chemical as well as a high heat resistance and extreme hardness are required from tools that are used in mechanical and automotive engineering or in plastics and building materials industry. Researchers at the Fraunhofer Institute for Ceramic Technologies and Systems IKTS in Dresden managed the production of complex hardmetal tools via 3D printing in a quality that are in no way inferior to conventionally produced high-performance tools.

Fraunhofer IKTS counts decades of proven expertise in the development of hardmetals. To date, reliable cutting, drilling, pressing and stamping tools made of...

Im Focus: Launch of New Industry Working Group for Process Control in Laser Material Processing

At AKL’16, the International Laser Technology Congress held in May this year, interest in the topic of process control was greater than expected. Appropriately, the event was also used to launch the Industry Working Group for Process Control in Laser Material Processing. The group provides a forum for representatives from industry and research to initiate pre-competitive projects and discuss issues such as standards, potential cost savings and feasibility.

In the age of industry 4.0, laser technology is firmly established within manufacturing. A wide variety of laser techniques – from USP ablation and additive...

Im Focus: New laser joining technologies at ‘K 2016’ trade fair

Every three years, the plastics industry gathers at K, the international trade fair for plastics and rubber in Düsseldorf. The Fraunhofer Institute for Laser Technology ILT will also be attending again and presenting many innovative technologies, such as for joining plastics and metals using ultrashort pulse lasers. From October 19 to 26, you can find the Fraunhofer ILT at the joint Fraunhofer booth SC01 in Hall 7.

K is the world’s largest trade fair for the plastics and rubber industry. As in previous years, the organizers are expecting 3,000 exhibitors and more than...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Experts from industry and academia discuss the future mobile telecommunications standard 5G

23.09.2016 | Event News

ICPE in Graz for the seventh time

20.09.2016 | Event News

Using mathematical models to understand our brain

16.09.2016 | Event News

 
Latest News

Chains of nanogold – forged with atomic precision

23.09.2016 | Life Sciences

New leukemia treatment offers hope

23.09.2016 | Health and Medicine

Self-assembled nanostructures hit their target

23.09.2016 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>