Combined approaches for increasing fetal hemoglobin (HbF) and de novo production of adult hemoglobin (HbA) in erythroid cells from β-thalassemia patients: treatment with HbF inducers and CRISPR-Cas9 based genome editing

Genome editing (GE) is one of the most efficient and useful molecular approaches to correct effects gene mutations in hereditary monogenetic diseases, including β-thalassemia. CRISPR-Cas9 has been proposed for effective correction β-thalassemia mutation, obtaining high-level “ de novo ” production adult hemoglobin (HbA). In addition primary causing β-thalassemia, several reports demonstrate that can be employed increase fetal (HbF), important clinical benefits treated patients. This objective achieved through disruption genes encoding transcriptional repressors γ-globin expression (such as BCL11A, SOX6, KLF-1 ) or their binding sites HBG promoter, mimicking non-deletional deletional HPFH mutations. These two (β-globin genome transcription) be, at least theory, combined. However, since multiplex associated with documented evidence concerning possible genotoxicity, this review focused on possibility combine pharmacologically-mediated HbF induction protocols HbA using editing.