At RNATICS, we believe in RNA therapeutics as an epochal breakthrough in medicine that will lead to the emergence of a third major class of drug molecules next to the established low molecular weight compounds and biologics.
RNA therapeutics exhibit key properties that overcome limitations inherent to conventional drug development:
- The number of molecules that are therapeutically addressable by RNA therapeutics is huge compared to conventional drugs and biologics that are directed towards a relatively small number of disease-relevant proteins. It includes the mRNAs of all proteins as well as thousands of non-coding RNAs (microRNAs, lncRNAs etc.) that are increasingly recognized as disease-relevant. In principle, highly specific inhibitors can be developed against all these RNAs.
- RNA therapeutic molecules are ‘programmable’, they are rationally designed and planned and can be rapidly synthesized on a large scale. Consequently, development of nucleic acid therapeutics can be achieved in a fraction of the time required for conventional drug development.
Nevertheless, efficient delivery (i.e. uptake into the target cell) and targeting (i.e. selectivity of drug uptake into specific cell types or organs) of RNA therapeutics remains an enormous technological challenge. Targeting into the liver, for example, is now successful using sugar ligand technology (in this case, N-acetylgalactosamine = GalNAc). Yet, targeting other organs remains a key challenge.
All human organs contain a population of tissue macrophages with key roles in tissue homeostasis and disease. These macrophages are critically involved in multiple inflammatory and fibrotic organ diseases with high medical need. At the same time, macrophages possess endogenous, unique phagocytic properties that enables rapid, high capacity uptake of foreign material. RNATICS’ proprietary targeting technology uses carbohydrate-coupling for efficient delivery of our RNA-based therapeutics to tissue macrophages and modulate their disease-causing activity. Our novel delivery pathway enables access to several organs beyond the liver offering tremendous therapeutic opportunities for multiple diseases.
RNATICS has developed first-in-class, macrophage-specific delivery technology for targeted RNA therapeutics. Cell surface receptors naturally present in high density on macrophages enable the targeted delivery to tissue resident macrophages through tailored carbohydrate ligands conjugated to the RNA therapeutic. The achievement of specific and efficient delivery to macrophages is a breakthrough technology that enables access to multiple tissues previously not accessible to RNA therapeutics.
The most advanced drug candidate based on RNATICS’ technology is a RNA therapeutic directed against a disease-causing microRNA in macrophages. The treatment is administered by inhalation directly to the damaged lungs of the patient and shows rapid, selective, and high-capacity delivery to tissue resident macrophages.
The underlying technology has been published in Nature Communications:
Beck, C., Ramanujam, D., Vaccarello, P., Widenmeyer, F. , Feuerherd, M., Cheng, C.-C., Bomhard, A., Abikeeva, T., Schädler, J., Sperhake, J.-P., Graw, M. , Safi, S., Hoffmann, H., Staab-Weijnitz, C. A., Rad, R., Protzer, U., Frischmuth, T. & Engelhardt, S. “Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage”. Nature Commununications (2023). DOI: 10.1038/s41467-023-40185-1.