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 Inselspital: Fewer CT scans needed after cerebral bleeding
20.03.2019 | Universitätsspital Bern

nachricht Building blocks for new medications: the University of Graz is seeking a technology partner
19.03.2019 | Karl-Franzens-Universität Graz

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: The taming of the light screw

DESY and MPSD scientists create high-order harmonics from solids with controlled polarization states, taking advantage of both crystal symmetry and attosecond electronic dynamics. The newly demonstrated technique might find intriguing applications in petahertz electronics and for spectroscopic studies of novel quantum materials.

The nonlinear process of high-order harmonic generation (HHG) in gases is one of the cornerstones of attosecond science (an attosecond is a billionth of a...

Im Focus: Magnetic micro-boats

Nano- and microtechnology are promising candidates not only for medical applications such as drug delivery but also for the creation of little robots or flexible integrated sensors. Scientists from the Max Planck Institute for Polymer Research (MPI-P) have created magnetic microparticles, with a newly developed method, that could pave the way for building micro-motors or guiding drugs in the human body to a target, like a tumor. The preparation of such structures as well as their remote-control can be regulated using magnetic fields and therefore can find application in an array of domains.

The magnetic properties of a material control how this material responds to the presence of a magnetic field. Iron oxide is the main component of rust but also...

Im Focus: Self-healing coating made of corn starch makes small scratches disappear through heat

Due to the special arrangement of its molecules, a new coating made of corn starch is able to repair small scratches by itself through heat: The cross-linking via ring-shaped molecules makes the material mobile, so that it compensates for the scratches and these disappear again.

Superficial micro-scratches on the car body or on other high-gloss surfaces are harmless, but annoying. Especially in the luxury segment such surfaces are...

Im Focus: Stellar cartography

The Potsdam Echelle Polarimetric and Spectroscopic Instrument (PEPSI) at the Large Binocular Telescope (LBT) in Arizona released its first image of the surface magnetic field of another star. In a paper in the European journal Astronomy & Astrophysics, the PEPSI team presents a Zeeman- Doppler-Image of the surface of the magnetically active star II Pegasi.

A special technique allows astronomers to resolve the surfaces of faraway stars. Those are otherwise only seen as point sources, even in the largest telescopes...

Im Focus: Heading towards a tsunami of light

Researchers at Chalmers University of Technology and the University of Gothenburg, Sweden, have proposed a way to create a completely new source of radiation. Ultra-intense light pulses consist of the motion of a single wave and can be described as a tsunami of light. The strong wave can be used to study interactions between matter and light in a unique way. Their research is now published in the scientific journal Physical Review Letters.

"This source of radiation lets us look at reality through a new angle - it is like twisting a mirror and discovering something completely different," says...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Modelica Conference with 330 visitors from 21 countries at OTH Regensburg

11.03.2019 | Event News

Selection Completed: 580 Young Scientists from 88 Countries at the Lindau Nobel Laureate Meeting

01.03.2019 | Event News

LightMAT 2019 – 3rd International Conference on Light Materials – Science and Technology

28.02.2019 | Event News

 
Latest News

Laser processing is a matter for the head – LZH at the Hannover Messe 2019

25.03.2019 | Trade Fair News

A Varied Menu

25.03.2019 | Life Sciences

‘Time Machine’ heralds new era

25.03.2019 | Information Technology

VideoLinks
Science & Research
Overview of more VideoLinks >>>