Cardiovascular applications for RNAs using integrated drug delivery systems

• Applicant: Professor Dr. Lars Mägdefessel
• Subject Area: Cardiology, Angiology ; Cardiac and Vascular Surgery
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 558565970

Cardiovascular diseases remain the most common causes of death worldwide. They include abdominal aortic aneurysms (AAA), which are characterized by their aortic dilation due to the disintegration of important structural components. If this disease has progressed far enough, it can lead to an acute rupture of the aorta, which is deadly in most cases. Currently, the only existing treatment option is surgical repair, open or endovascular, however, this can be quite risky for the average patient at an advanced age. Similarly, patients with a smaller, yet fast-progressing AAA, which are currently not considered suitable candidates for an intervention, could be offered with a less-invasive treatment. One possibility for future treatment approaches is the modulation of disease-relevant non-coding RNAs. Here, disease-promoting genes and their transcripts within the vessel wall can be specifically inhibited to slow down or completely halt the progression of the disease. However, clinical studies to date have solely focused on the systemic administration of RNA therapeutics. This approach requires very high quantities of an RNA inhibitor (siRNA, Antisense Oligonucleotide), which becomes very expensive with the likely occurrence for 'off-target' effects in tissues and organs in which RNA therapies assimilate to a higher extent (e.g., liver or kidney). The proposed project therefore aims to develop an effective local application for patients with vascular diseases. The special carrier matrix, which is intended to protect the active RNA-targeting molecule, while still guaranteeing a high level of biocompatibility being particularly important in this context. In addition, the therapeutic agent will be encapsulated in lipid nanoparticles for better absorption and reagent stability. The combination of encapsulation and optimized carrier matrix will thus ensure lesser quantities of the active RNA-based therapy being required, making the project more translatable into clinical applications. We are convinced that our approach will represent a very promising alternative to the systemic administration of RNA therapies currently used, as it will result in better tissue penetration and less off-target effects in patients suffering from vascular diseases.

• DFG Programme: Research Grants (Transfer Project)
• Application Partner: InnoRA GmbH
• Cooperation Partner: Dr.-Ing. Christoph Hein