MUNICH, Germany — What if a spray for the lungs could prevent damage from infections like COVID-19? Researchers at the Technical University of Munich (TUM) have developed such an inhaler using RNA technology. The innovative approach uses a new sugar-based transport mechanism to deliver the therapeutic agent effectively to its target.
The research team created an RNA-based compound known as RCS-21, designed to combat severe lung inflammation and fibrosis, which refers to the scarring of lung tissue, as seen in diseases like SARS-CoV2 infections — the virus causing COVID. Inside cells, RCS-21 works by inhibiting the action of a molecule called microRNA 21. This nucleic acid is a key trigger for the excessive activity of macrophages during severe lung infections.
The breakthrough lies in the unique delivery mechanism. Through inhalation using an inhaler, the RCS-21 compound effectively reaches the overly active immune cells responsible for the inflammation. The researchers exploited a distinctive feature of macrophages, cells that play a role in lung health by rapidly eliminating bacteria and fungal spores. These scavenger cells identify their targets partly through complex sugar molecules on the invaders’ surfaces.
“We’ve discovered through single cell analyses that these sugar receptors are abundant on macrophages, which is quite unique to them and hardly present elsewhere,” says Stefan Engelhardt, a professor of Pharmacology and Toxicology at TUM, in a university release. “On the other hand, the receptors are, in a sense, a unique feature of macrophages – they hardly occur anywhere else.”
The researchers linked the active RCS-21 compound to a sugar molecule, specifically trimannose. While such an approach had previously been attempted with less complex compounds, this innovative strategy yielded promising results in mouse studies. The spray delivery method significantly enhanced the uptake of the therapeutic agent by macrophages due to the inclusion of sugar molecules.
In tests with mice, RCS-21 was able to reduce microRNA 21 levels by over 50 percent compared to untreated animals. Additionally, inflammation and fibrosis were substantially diminished after treatment. This innovative approach also effectively suppressed increased microRNA-21 activity in human lung tissue samples infected with the SARS-CoV-2 coronavirus.
“This technology opens up a wide field for the development of novel RNA-based drugs. I expect a lot to happen in this area in the next few years,” says Engelhardt.
Clinical trials are on the horizon, with RNATICS, a TUM spin-off, spearheading the initiative. The startup received substantial funding from the German Federal Ministry of Education and Research (BMBF) to support the drug’s development. Clinical trials in humans are set to commence in 2024, offering hope for a breakthrough in lung treatment and potential advances in RNA-based drugs.
The study is published in the journal Nature Communications.
