Advanced nucleic acid therapeutics for targeted lung disease treatment

Team: Dr. Aman Ishaqat, Emma Buller, Tatiana Abikeeva, Anton Bomhard, Hannah Britzelmeier, Sabine Brummer, Alora Marks, Mehmet Durmaz, Dr. Claudia Klug, PD Dr. Andrea Welling

Lung diseases, including acute (e.g., idiopathic pulmonary fibrosis) and chronic (e.g., chronic obstructive pulmonary disease), pose a significant global health burden. These conditions are marked by inflammation, tissue remodelling, and progressive airflow limitations. Macrophages, central players in the innate immune system, are critical in driving lung disease pathology. Current treatments focus on symptom relief but fail to halt disease progression, emphasizing the need for advanced therapies.

Nucleic acid therapeutics represent a rapidly advancing field, offering the potential to target "undruggable" genes with faster and more cost-effective development compared to traditional therapies. Despite their promise, challenges such as degradation, delivery, and minimizing immunogenicity remain. To address these, our research aims to develop nucleic acid-based therapies that target pulmonary macrophages via mannose receptor 1 (MRC1), using inhalation to ensure macrophage-specific delivery while reducing off-target effects. This approach seeks to inhibit disease-related upregulated genes in macrophages, improving lung function and reducing inflammation and fibrosis, offering a novel therapeutic strategy for both acute and chronic lung diseases with high translational potential.