Pulmonary Delivery of Messenger RNA (mRNA) Therapeutics for Respiratory Diseases

Abstract

With the advances in biotechnology, messenger RNA (mRNA) therapeutics have provided new and exciting opportunities for the treatment and prevention of a wide range of respiratory diseases. The potential applications of mRNAs include lung infections, genetic disorders (e.g., cystic fibrosis), inflammatory diseases (e.g., asthma), and vaccines. However, the development of mRNA therapeutics is hindered by its delivery and cellular uptake due to its large molecular size, high negative charge, hydrophilicity, and poor stability. Currently, the administration of mRNA therapeutics is limited to parenteral injection. Pulmonary delivery offers the advantages of non-invasive route of administration and direct application of mRNA at the site of action in the lung so that a lower dose is required with reduced systemic toxicity. A variety of delivery platforms are being developed to deliver mRNA therapeutics for lung diseases through the pulmonary route. This chapter summarizes and discusses (i) different delivery strategies, including lipid nanoparticles (LNPs), polymers, peptides, and chemical modification for pulmonary mRNA delivery; and (ii) the potential clinical applications of inhaled mRNA therapies.