In many clinically-approved nucleic acid products, transfection agents, including viral vectors and lipid nanoparticles, have been applied for high transfection efficiency, whereas they have major concerns about severe systemic adverse action. Inhaled dry powder formulations for naked nucleic acids without transfection agents are highly attractive because of many practical advantages, such as direct and noninvasive delivery to the lungs where nuclease activity is low, easy usage, good device portability, and high storage stability. However, various physical stresses generated in the production process can destabilize nucleic acids, and there are few articles demonstrating the efficacy of the naked nucleic acid powders produced. The present article introduces our outcomes about the stability of naked nucleic acids under several types of physical treatment or powder formation and about the successful development of inhaled dry naked nucleic acid powders with high aerosol performance and superior pulmonary transfection efficiency.