Recent strategies for enhanced delivery of mRNA to the lungs.

mRNA-based therapies have emerged as a transformative tool in modern medicine, gaining significant attention following their successful use in COVID-19 vaccines. Delivery to the lungs offers several compelling advantages for mRNA delivery. The lungs are one of the most vascularized organs in the body, which provides an extensive surface area that can facilitate efficient drug transport. Local delivery to the lungs bypasses gastrointestinal degradation, potentially enhancing therapeutic efficacy. In addition, the extensive capillary network of the lungs provides an ideal target for systemic delivery. However, developing effective mRNA therapies for the lungs presents significant challenges. The complex anatomy of the lungs and the body's immune response to foreign particles create barriers to delivery. This review discusses key approaches for overcoming these challenges and improving mRNA delivery to the lungs. It examines both local and systemic delivery strategies aimed at improving lung delivery while mitigating off-target effects. Although substantial progress has been made in lung-targeted mRNA therapies, challenges remain in optimizing cellular uptake and achieving therapeutic efficacy within pulmonary tissues. The continued refinement of delivery strategies that enhance lung-specific targeting while minimizing degradation is critical for the clinical success of mRNA-based pulmonary therapies.