Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Hyperactive "Sleeping Beauty" - MDC Scientists: "Optimized Tool for Gene Delivery"

04.05.2009
Scientists from the Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch, Germany have succeeded in generating a hyperactive "jumping gene" (a transposon) and hope to have an improved tool for basic research and gene therapy.

"The new transposon system is able to introduce genes into cells and to stably insert them into the cell's genome at an unprecedented efficiency," Dr. Lajos Mátés, Dr. Zoltán Ivics and Dr. Zsuzsanna Izsvák point out. They worked together with scientists from the Catholic University of Leuven, Belgium (Nature Genetics, doi: 10.1038/ng.343).*

Transposable elements are molecular parasites that propagate themselves in genomes. But at the same time they provide plasticity to the genome that clearly contributed to the evolution of gene function across the tree of life. About half of the human genome is derived from ancient transposable element sequences, Dr. Izsvák remarks.

However, due to mutations, the vast majority of the transposons became inactivated. Based on transposons in fish that are presumed to have been active approximately 20 million years ago, Dr. Ivics and Dr. Izsvák resurrected a jumping gene more than ten years ago. They named the transposon Sleeping Beauty, because they literally awakened it after a long evolutionary "sleep".

With their new tool, they were able to introduce genes into cells of vertebrates which was impossible before, as researchers previously lacked efficient transposon technologies to do so. However, the efficiency of the new transposon remained limited in some cells, such as stem cells.

Hundredfold Increase in Sleeping Beauty's Activity
The scientists solved this problem by slightly changing the genetic code of Sleeping Beauty, resulting in a hundredfold increase in its activity. Now, a transferred gene (transgene) finds its way into the cell's genome more easily. "Our hyperactive Sleeping Beauty is safer, easier, and cheaper than any other method before," says Dr. Izsvák.

Currently, scientists use disarmed viruses or a variety of non-virus based methods to get genes into cells. However, these methods are either too dangerous or too inefficient for broad application in gene therapy. Experiments with the new transposon system in mice showed that transgenes enter the genome safely and are stably integrated, says Dr. Ivics. Even after a year, the genes were still active.

The MDC researchers hope that their new tool is going to become the new standard method to introduce genes into cells. "Already this year, the first clinical trial with the transposon developed in our lab shall take place in the USA", says Dr. Ivics. According to him, Sleeping Beauty will be used to transport a therapeutic gene into isolated immune cells (T cells). These altered cells will then be used to treat a specific form of cancer (B-lymphoid malignancies) in patients.

The research is part of a project funded by the European Union and coordinated by the MDC. Together with nine partners from seven European countries, the MDC-researchers seek for novel, nonviral technologies for therapeutic gene delivery.

*Molecular Evolution of a Novel Hyperactive Sleeping Beauty Transposase Enables Robust Stable Gene Transfer in Vertebrates

Lajos Mátés1,*, Marinee K. L. Chuah2,*, Eyayu Belay2, Boris Jerchow1, Namitha Manoj1, Abel Acosta-Sanchez2, Dawid P. Grzela1, Andrea Schmitt1, Katja Becker1, Janka Matrai2, Ling Ma2, Esmira Samara-Kuko2, Cony Gysemans5, Diana Pryputniewicz1, Csaba Miskey1, Bradley Fletcher3, Thierry VandenDriessche2, Zoltán Ivics1 and Zsuzsanna Izsvák1,4

* Contributed equally
1 Max Delbrück Center for Molecular Medicine, Berlin, Germany
2 Flanders Institute for Biotechnology (VIB), Vesalius Research Center, University of Leuven, Leuven, Belgium
3 Department of Pharmacology and Therapeutics, University of Florida, College of Medicine, Gainesville, FL 32610-0267, USA.
4 Institute of Biochemistry, Biological Research Center of the Hungarian Academy of Sciences, Szeged, Hungary

5 Department of Experimental Medicine, Laboratory for Experimental Transplantation, University of Leuven, Belgium

Barbara Bachtler
Press and Public Affairs
Max Delbrück Center for Molecular Medicine (MDC) Berlin-Buch
Robert-Rössle-Straße 10; 13125 Berlin; Germany
Phone: +49 (0) 30 94 06 - 38 96
Fax: +49 (0) 30 94 06 - 38 33
e-mail: presse@mdc-berlin.de

Barbara Bachtler | Max-Delbrück-Centrum
Further information:
http://www.mdc-berlin.de
http://www2.mdc-berlin.de/izsvak/eng/pages/disclaimer.htm

More articles from Life Sciences:

nachricht Navigational view of the brain thanks to powerful X-rays
18.10.2017 | Georgia Institute of Technology

nachricht Separating methane and CO2 will become more efficient
18.10.2017 | KU Leuven

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Osaka university researchers make the slipperiest surfaces adhesive

18.10.2017 | Materials Sciences

Space radiation won't stop NASA's human exploration

18.10.2017 | Physics and Astronomy

Los Alamos researchers and supercomputers help interpret the latest LIGO findings

18.10.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>