Intelligent siRNA molecules for cell-specific breast cancer therapy
Dr. Tobias Pöhlmann
Institute of Organic Chemistry and Macromolecular Chemistry, Friedrich Schiller University Jena
Recipient: Friedrich Schiller University Jena
Funding: GO-Bio Phase I (01.05.2011 - 30.04.2016, 3.253.463 Euro)
The selective switching off of genes using RNA interference has great potential for the treatment of diseases that were previously difficult or even impossible to treat. The method is based on small RNA molecules, so-called ‘small interfering RNAs’ (siRNAs) that can be deployed to targetedly interrupt the process of protein production. In the past few years, however, the euphoria that initially surrounded the use of small RNAs in medicine has been dampened by a series of setbacks. Here, the main issue has been the lack of accuracy of the small RNA molecules. A central challenge in the field of drug discovery is thus the targeted transport of the RNAs to those locations in the body where they are intended to function.
This is the starting point for the ‘Intelligent siRNA’ technology developed by Tobias Pöhlmann and his team. This involves the attachment of peptides to the siRNA molecules in the manner of a pair of handcuffs. Once blocked in this way, the siRNAs have no initial effect and are only activated when the peptide-bound siRNA molecules encounter so-called ‘peptidases’ in specific cells. The enzymes function as the correct key for the handcuffs, liberating the RNA molecules to do their job. Tumour tissue or virus-infected cells exhibit specific peptidases, which can serve as ‘enzyme keys’ and thus enable the tailored production of intelligent siRNAs for these sites. Thanks to high cell specificity, it is even possible to specifically deploy the siRNAs as a form of cell poison, for example for the destruction of tumour cells.
In the GO-Bio project, the Jena-based team is planning the development of a targeted breast cancer therapy that utilises their intelligent RNA molecules. This will encompass the preclinical testing of the customised siRNAs as well as the establishment of GMP production of active ingredients. The founding of the company ‘BianoScience’, which will offer the technology in the form of kits for the research market, is planned for this year.