RNA-mediated immunostimulation

In the last years it has been recognized that RNA serves more functions than merely transducing information (mRNA, rRNA). First, it has been discovered that double-stranded RNA intermediates regulate endogenous RNA stability which is referred to as RNA interference. This process can be mimicked by synthetic small inhibitory RNA (siRNA) which now develops as a powerful molecular tool for the examination of gene functions (siRNA knockdown). Second, RNA has been found to directly degradates mRNA specifically (microRNA, miRNA) and thirdly RNA has also been recognized to be a target for immune recognition mechanisms especially in viral infections. Thus, RNA can induce activation of immune cells.

Some of the "new" functions (RNA interference and RNA stimulation) are interconnected. We identified the structural needs by which immune receptors recognize RNA. This is important for the use of siRNA in various settings including medical¬therapeutical approaches.

We have developed tools to interfere with TLR-dependent recognition of oligonucleotides as well as means to introduce siRMǸA or miRNA into primary cells.

Selected publications

1. Ziegler, S., M. E. Eberle, S. J. Wölfle, K. Heeg, and I. Bekeredjian-Ding. 2013. Bifunctional Oligodeoxynucleotide/AntagomiR Constructs: Evaluation of a New Tool for MicroRNA Silencing. Nucleic Acid Therapeutics 23: 427–434.
2. Heeg, K., A. Dalpke, M. Peter, and S. Zimmermann. 2008. Structural requirements for uptake and recognition of CpG oligonucleotides. Int. J. Med. Microbiol. 298: 33–38.
3. Eberle, F., K. Giessler, C. Deck, K. Heeg, M. Peter, C. Richert, and A. H. Dalpke. 2008. Modifications in small interfering RNA that separate immunostimulation from RNA interference. The Journal of Immunology 180: 3229.