Sickle cell anemia is the most common heritable hematological disease, yet no curative treatment exists for this disorder. Moreover, the intricacies of globin gene expression have made the development of treatments for hemoglobinopathies based on gene therapy difficult. An alternative genetic approach to sickle cell therapy is based on RNA repair. A trans-splicing group I ribozyme was used to alter mutant β-globin transcripts in erythrocyte precursors derived from peripheral blood from individuals with sickle cell disease. Sickle β-globin transcripts were converted into messenger RNAs encoding the anti-sickling protein γ-globin. These results suggest that RNA repair may become a useful approach in the treatment of genetic disorders.