Challenges for inhaled gene therapy and biologics include stability, cellular uptake, aerosolization, targeted delivery, and industrial-scale production. Examples of inhaled new modalities range from monoclonal and fragment antibodies to peptides and vaccines, illustrating the diverse applications in respiratory conditions. Research and clinical trials are ongoing to explore the potential of inhaled RNA therapeutics for various respiratory conditions, including mRNA-based therapeutics and oligonucleotides (ASOs, miRNA, siRNA), although these therapies are still in the research and development phase and have not yet received regulatory approval for clinical use.
The field of RNA therapeutics has made significant strides, notably with the approval of Onpattro™, a siRNA therapy, and the introduction of lipid nanoparticle (LNP)-enabled mRNA vaccines for COVID-19. However, ensuring stability in RNA drug distribution using non-viral delivery systems, especially in areas without cold chain storage, remains a challenge. The presentation will include a proof-of-concept study for engineering an LNP mRNA formulation suitable for spray drying, resulting in a stable dry powder formulation preserving mRNA functionality. Intratracheal delivery of spray dried LNPs loaded with eGFP mRNA to rats demonstrated the production of the eGFP protein in cell types involved in adaptive immunity, highlighting the potential for inhaled vaccines against respiratory pathogens. These findings suggest that spray drying of LNPs enhances their stability and may enable RNA delivery to the lung for various therapies. The study underscores the pivotal role of LNPs in addressing the challenges of RNA therapeutics and emphasizes the potential of inhaled gene therapy and biologics from an industrial perspective.