Chen et al. report in Science a nonviral strategy for treating cystic fibrosis caused by nonsense mutations. The team engineered suppressor tRNAs and delivered them to the lung using inhaled lipid nanoparticles. In CF bronchial cells, mouse models, and patient-derived organoids, the treatment enabled readthrough of premature stop codons and restored full-length CFTR protein and channel function. The approach could be applicable to other genetic disorders caused by nonsense variants. A key limitation is dose-dependent pulmonary inflammation associated with lipid nanoparticle delivery, which will need to be addressed before clinical translation. (https://www.science.org/doi/10.1126/science.aeb0054)