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:
Dr. Carsten Rudolph | EurekAlert!
Antimicrobial substances identified in Komodo dragon blood
23.02.2017 | American Chemical Society
New Mechanisms of Gene Inactivation may prevent Aging and Cancer
23.02.2017 | Leibniz-Institut für Alternsforschung - Fritz-Lipmann-Institut e.V. (FLI)
In the field of nanoscience, an international team of physicists with participants from Konstanz has achieved a breakthrough in understanding heat transport
Cells need to repair damaged DNA in our genes to prevent the development of cancer and other diseases. Our cells therefore activate and send “repair-proteins”...
The Fraunhofer IWS Dresden and Technische Universität Dresden inaugurated their jointly operated Center for Additive Manufacturing Dresden (AMCD) with a festive ceremony on February 7, 2017. Scientists from various disciplines perform research on materials, additive manufacturing processes and innovative technologies, which build up components in a layer by layer process. This technology opens up new horizons for component design and combinations of functions. For example during fabrication, electrical conductors and sensors are already able to be additively manufactured into components. They provide information about stress conditions of a product during operation.
The 3D-printing technology, or additive manufacturing as it is often called, has long made the step out of scientific research laboratories into industrial...
Nature does amazing things with limited design materials. Grass, for example, can support its own weight, resist strong wind loads, and recover after being...
Nanometer-scale magnetic perforated grids could create new possibilities for computing. Together with international colleagues, scientists from the Helmholtz Zentrum Dresden-Rossendorf (HZDR) have shown how a cobalt grid can be reliably programmed at room temperature. In addition they discovered that for every hole ("antidot") three magnetic states can be configured. The results have been published in the journal "Scientific Reports".
Physicist Dr. Rantej Bali from the HZDR, together with scientists from Singapore and Australia, designed a special grid structure in a thin layer of cobalt in...
13.02.2017 | Event News
10.02.2017 | Event News
09.02.2017 | Event News
23.02.2017 | Physics and Astronomy
23.02.2017 | Earth Sciences
23.02.2017 | Life Sciences