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 Satellites, airport visibility readings shed light on troops' exposure to air pollution
09.12.2016 | Veterans Affairs Research Communications

nachricht Oxygen can wake up dormant bacteria for antibiotic attacks
08.12.2016 | Penn State

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: Electron highway inside crystal

Physicists of the University of Würzburg have made an astonishing discovery in a specific type of topological insulators. The effect is due to the structure of the materials used. The researchers have now published their work in the journal Science.

Topological insulators are currently the hot topic in physics according to the newspaper Neue Zürcher Zeitung. Only a few weeks ago, their importance was...

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Researchers identify potentially druggable mutant p53 proteins that promote cancer growth

09.12.2016 | Life Sciences

Scientists produce a new roadmap for guiding development & conservation in the Amazon

09.12.2016 | Ecology, The Environment and Conservation

Satellites, airport visibility readings shed light on troops' exposure to air pollution

09.12.2016 | Health and Medicine

VideoLinks
B2B-VideoLinks
More VideoLinks >>>