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Save messengers -- modified mRNAs open up new therapeutic possibilities
Date:2/7/2011

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 mRNA
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Contact: Dr. Carsten Rudolph
Carsten.Rudolph@med.uni-muenchen.de
49-895-160-7711
Ludwig-Maximilians-Universitt Mnchen
Source:Eurekalert

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