New drugs for use in regenerative medicine
Bioproducts synthesized by biotechnological methods based on the use of genetically altered organisms are becoming increasingly important in clinical practice. So far, most clinical applications have involved the use of synthetic genes or their protein products. However, both of these approaches suffer from serious disadvantages. Gene-based therapies entail poorly defined biological risks and pose technical challenges that have not yet been adequately addressed. Proteins, on the other hand, have a short biological half-life, which limits their clinical effectiveness, and increases manufacturing and treatment costs.
A new class of therapeutics promises to avoid these drawbacks. A team of researchers led by LMU pharmacologist Carsten Rudolph is working on modified messenger RNAs (mRNAs are biomolecules related to DNA that direct the synthesis of specific proteins in cells) and hopes to make them suitable for use in the clinical setting. The researchers have synthesized chemically modified RNA molecules that are highly robust and do not induce an immune response. “By chemically modifying the mRNAs, we can largely avoid the activation of the immune system that they might otherwise provoke, so that no inflammatory reactions ensue,” says Rudolph. “The modified mRNAs – in contrast to conventional mRNAs – can therefore be administered repeatedly. Furthermore, they are chemically more stable, so that they are effective at very low doses.” These stable, non-immunogenic mRNAs (SNIM-RNAs) can be introduced as uncoated molecules into selected cells or tissues, where they are used for the manufacture of the required therapeutic protein. In a mouse model system, Rudolph and his colleagues have already confirmed the therapeutic potential of the new approach. In their prize-winning GO-Bio project, they now plan, in collaboration with Plank, to develop the strategy further, specifically for use in regenerative medicine. The intention is to design and manufacture bioactive materials that can serve as carriers, and to test them in animal models. These could be coated with SNIM-RNA and implanted to promote and accelerate healing and repair of damaged tissue. It is hoped that this work will provide a secure basis for clinical studies to be initiated in the near future.
Carsten Rudolph is a pharmacologist and heads the Research Group in Experimental Gene Therapy at LMU Munich University Hospital. He and Christian Plank founded the company ethris GmbH in 2009 to commercialize the SNIM-RNA technology. In 2005, Rudolph won the BMBF’s BioFuture Award for his work. The aim of the GO-Bio scheme is to facilitate the transformation of research findings of potentially high value into economically exploitable products. By accelerating the pre-commercial development phase and helping to increase marketability, the gap between basic scientific research and commercial application can be narrowed. (göd/PH)
PD Dr. Carsten Rudolph
Research Center of the Pediatric Clinic and Outpatient Clinic in the Dr. von Hauner Children‘s Hospital
Medical Center of the University of Munich
Phone +49 (0) 89 / 5160 - 7711