Gene editing by the CRISPR-Cas9 nuclease system technology can be considered among the most promising strategies to correct hereditary mutations in a variety of monogenic diseases. In this paper, we present for the first time the correction, by CRISPR-Cas9 gene editing, of the b 0 39-thalassemia mutation, one of the most frequent in the Mediterranean area. The results obtained demonstrated the presence of normal b-globin genes after CRISPR-Cas9 correction of the b 0 39-thalassemia mutation performed on erythroid precursor cells from homozygous b 0 39-thalassemia patients. This was demonstrated by allelespecific PCR and sequencing. Accumulation of corrected b-globin mRNA and relevant "de novo" production of b-globin and adult hemoglobin (HbA) were found with high efficiency. The CRISPR-Cas9-forced HbA production levels were associated with a significant reduction of the excess of free a-globin chains. Genomic toxicity of the editing procedure (low indels and no off-targeting) was analyzed. The protocol might be the starting point for the development of an efficient editing of CD34 + cells derived from b 0 39 patients and for the design of combined treatments using, together with the CRISPR-Cas9 editing of the b-globin gene, other therapeutic approaches, such as, for instance, induction of HbA and/or fetal hemoglobin (HbF) using chemical inducers.