Introduction: Lipid nanoparticles (LNPs) have revolutionized nucleic acid delivery, predominantly targeting the liver following systemic administration. However, safe and efficacious pulmonary delivery of mRNA by LNPs inhalation remains a significant challenge (1). As a result, gene therapy for lung diseases like α-1 antitrypsin deficiency, cystic fibrosis. and chronic obstructive pulmonary disease (COPD) has been an unmet need (2). Herein, we demonstrate the preclinical success of delivering mRNA LNPs to the lungs via nebulization.
Learning Objectives:
Explain key challenges and motivations for pulmonary delivery of mRNA using LNPs.
Describe the formulation and nebulization approach used to generate and deliver mRNA‑LNPs.
Evaluate preclinical performance of nebulized mRNA‑LNPs in terms of LNP expression efficiency, and safety.
