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GRK 1202:  Oligonucleotides in Cell Biology and Therapy

Subject Area Medicine
Term from 2005 to 2014
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 820988
 
Oligonucleotides are small polymeric DNA or RNA molecules. This Research Training Group combines two important current developments:
-- immunologically active oligonucleotides that control the immune system
-- RNA interference (siRNA, small interfering RNA) to selectively knock-down gene expression
It is our goal to develop innovative strategies for the therapy of cancer, infection and autoimmunity by selectively controlling the immune system and inhibiting target gene expression.
Immunostimulatory oligonucleotides and siRNA embody a substantial increase in possibilities, to both understand and therapeutically manipulate disease processes. By administration of immunologically active oligonucleotides it has become possible to stimulate the innate immune system with a synthetic compound mimicking viral infection. It has become recognised recently, that the innate immune system employs a family of receptors (Toll-like-receptors, TLR) to detect characteristic patterns within viral nucleic acids. This covers so-called CpG-motifs within viral DNA and certain conformations of single-stranded and double-stranded RNA. Synthetic oligonucleotides containing these motifs can now be employed to selectively induce an immune response against virus-infected host cells (interferon-?). This type of immune response (Th1) is essential for the successful immunotherapy of cancer. Up to now, mainly bacterial compounds like LPS have been available to stimulate innate immune responses; yet therapeutic administration is limited due to toxicity.
Application of siRNA is based on a fundamentally different mechanism: siRNA consists of short double-stranded RNA-molecules, containing one strand that is complementary to the mRNA of a target gene. Using siRNA it is possible to selectively knock-down genes at the post-transcriptional level, that play key roles in the development of disease.
The Research Training Group integrates nine research groups of the university to an internationally oriented competitive education unit. The participation of the medical faculty as well as the faculty of natural sciences and groups with focus on immunology, molecular biology and biophysics guarantees a high degree of interdisciplinarity.
DFG Programme Research Training Groups
 
 

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