What’s in the future of inhaled RNA?
Olivia M. Merkel1,2
1Ludwig-Maximilians-Universität München, Butenandtstraße 5, 81377 Munich, Germany
2RNhale GmbH, Kidlerstraße 20, 81371 Munich, Germany
Summary
RNA-based medicines, while promising, encounter delivery obstacles, particularly outside the liver due to degradation and accumulation issues. Our research focuses on developing a dry powder platform for RNA nanoparticles via spray-drying, aiming to enhance stability and broaden organ targeting beyond the liver. Our approach seeks to improve RNA medicines by creating inhalable dry powder formulations. This technology could overcome current limitations, ensuring direct access to the lungs, reduced variability in manufacturing, and enhanced stability.
We’re refining protocols to increase RNA content in powder doses and experimenting with various excipients to safeguard particles during spray-drying. In vivo studies are evaluating lung residence, gene expression, safety, and toxicity of these formulations. Through in vitro infection models, especially against viruses like SARS-CoV-2, we’ve seen promising results in gene silencing and reduced viral RNA levels. Additionally, our biodistribution studies use nuclear imaging techniques and animal models to establish dosing regimens that optimize lung retention while minimizing off-target effects.
For effective lung cell targeting, we engineer shielded nanocarriers adorned with specific ligands to enhance cell uptake while avoiding mucus interactions.
Ultimately, our goal is to create stable RNA nanoparticle formulations suitable for inhalation, expanding their therapeutic reach beyond the liver. This could potentially revolutionize the treatment of challenging lung diseases, benefiting society, not least in developing countries.
This summary captures the essence of our work in developing inhalable RNA formulations aimed at enhancing stability and efficacy while broadening their application for treating lung diseases.