Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Save messengers -- modified mRNAs open up new therapeutic possibilities

08.02.2011
Defects in the genome are the cause of many diseases. Gene therapy – direct replacement of mutant genes by intact DNA copies – offers a means of correcting such defects.

Now a research team based at the Medical Center of the University of Munich, and led by Privatdozent Dr. Carsten Rudolph, has taken a new approach that avoids DNA delivery. The team shows for the first time that chemical modification of mRNAs (the metabolically active molecules derived from genomic DNA that programs protein synthesis) provides a promising alternative to DNA-based procedures.

In contrast to the latter, the modified RNAs do not increase the risk of cancer, and do not induce frequently observed severe immune reactions seen with DNA or unmodified mRNA. The researchers show that the new method is life-saving in mice with a congenital lethal lung defect. "These results clearly demonstrate the therapeutic potential of our mRNAs," says Rudolph. (Nature Biotechnology, 7 February 2011)

Gene therapy offers great potential for the treatment of both congenital and acquired diseases that are otherwise not amenable to other treatments. However, the approaches that have been tested so far are associated with serious side-effects. The use of engineered viruses to introduce intact genes into the cellular genome are associated with an increased risk of developing leukaemia, and can provoke strong immune reactions. Nonviral vectors, on the other hand, tend to be inefficient delivery vehicles. The new RNA-based method displays neither of these disadvantages. "Chemical modification of the mRNA prevents it from activating the immune system, so that no inflammatory reaction ensues," says Rudolph. "Furthermore, in contrast to conventional mRNA, the modified mRNA can be administered repeatedly, is more stable and is effective at very low doses."

The new method, referred to as Transcript Therapy by its inventors, opens up new opportunities for targeted treatments. The modified mRNAs shuttle genetic information into cells in a form that can be used directly for the production of therapeutically active proteins. In addition to their potential for the treatment of genetic diseases, they represent an alternative to established protein-based treatment regimes. The researchers demonstrated the efficacy of the latter application in a mouse model. A single intramuscular injection of mRNAs coding for the hormone erythropoetin, which stimulates the differentiation of red blood cells, led to a significant increase in erythrocyte counts four weeks later.

The team also employed a mouse model to show that the technique can effectively be used to treat a genetic disease. For this, they chose a strain with a lethal congenital lung defect, caused by its inability to make surfactant protein B (SP-B). Regular application of mRNA for SP-B, as an aerosol, to the lungs of the mutant mice restored lung function, and the effect persisted for the duration of the study. Rudolph sees great scope for transcript therapy in regenerative medicine and the treatment of metabolic diseases, and hopes to test the efficacy of modified mRNAs in a clinical setting over the next few years.

Publication:
Expression of therapeutic proteins after delivery of chemically modified mRNA in mice
Kormann MS, Hasenpusch G, Aneja MK, Nica G, Flemmer AW, Herber-Jonat S, Huppmann M, Mays LE, Illenyi M, Schams A, Griese M, Bittmann I, Handgretinger R, Hartl D, Rosenecker J, Rudolph C.
Nature Biotechnology, XX. February 2011
doi: 10.1038/nbt.1733

Dr. Carsten Rudolph | EurekAlert!
Further information:
http://www.uni-muenchen.de

More articles from Life Sciences:

nachricht Nesting aids make agricultural fields attractive for bees
20.07.2017 | Julius-Maximilians-Universität Würzburg

nachricht The Kitchen Sponge – Breeding Ground for Germs
20.07.2017 | Hochschule Furtwangen

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Manipulating Electron Spins Without Loss of Information

Physicists have developed a new technique that uses electrical voltages to control the electron spin on a chip. The newly-developed method provides protection from spin decay, meaning that the contained information can be maintained and transmitted over comparatively large distances, as has been demonstrated by a team from the University of Basel’s Department of Physics and the Swiss Nanoscience Institute. The results have been published in Physical Review X.

For several years, researchers have been trying to use the spin of an electron to store and transmit information. The spin of each electron is always coupled...

Im Focus: The proton precisely weighted

What is the mass of a proton? Scientists from Germany and Japan successfully did an important step towards the most exact knowledge of this fundamental constant. By means of precision measurements on a single proton, they could improve the precision by a factor of three and also correct the existing value.

To determine the mass of a single proton still more accurate – a group of physicists led by Klaus Blaum and Sven Sturm of the Max Planck Institute for Nuclear...

Im Focus: On the way to a biological alternative

A bacterial enzyme enables reactions that open up alternatives to key industrial chemical processes

The research team of Prof. Dr. Oliver Einsle at the University of Freiburg's Institute of Biochemistry has long been exploring the functioning of nitrogenase....

Im Focus: The 1 trillion tonne iceberg

Larsen C Ice Shelf rift finally breaks through

A one trillion tonne iceberg - one of the biggest ever recorded -- has calved away from the Larsen C Ice Shelf in Antarctica, after a rift in the ice,...

Im Focus: Laser-cooled ions contribute to better understanding of friction

Physics supports biology: Researchers from PTB have developed a model system to investigate friction phenomena with atomic precision

Friction: what you want from car brakes, otherwise rather a nuisance. In any case, it is useful to know as precisely as possible how friction phenomena arise –...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

»We are bringing Additive Manufacturing to SMEs«

19.07.2017 | Event News

The technology with a feel for feelings

12.07.2017 | Event News

Leipzig HTP-Forum discusses "hydrothermal processes" as a key technology for a biobased economy

12.07.2017 | Event News

 
Latest News

Researchers create new technique for manipulating polarization of terahertz radiation

20.07.2017 | Information Technology

High-tech sensing illuminates concrete stress testing

20.07.2017 | Materials Sciences

First direct observation and measurement of ultra-fast moving vortices in superconductors

20.07.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>