Mutations in the β-globin (HBB) gene are the cause of β-hemoglobinopathies, which are one of the most common autosomal recessive inherited monogenic disorder in the world. Modern genome editing technologies such as CRISPR/Cas9 allow us to edit hematopoietic stem cells (HSCs) in a way they can be used to treat disorders like sickle cell anemia and β-thalassemia, which represent a growing health problem. The editing strategy is based on collecting patient's own HSCs and perform editing ex vivo. The main rearrangement strategies are: correction of the mutation responsible for the disease in the HBB gene by homologous recombination or reactivation of γ-globin expression, which enables formation of fetal hemoglobin; this is achieved by inducing mutations in the main regulator of γ-globin formation - BCL11A or in its erythroid-specific enhancers. After gene editing, the successfully edited cells are transplanted back into the patient. It is also possible to use allogeneic transplantation, where healthy cells of a histocompatible donor are transplanted into the patient. Simple isolation and collection of HSCs have enabled the advancement of genetic therapies all the way to clinical trials with promising results.
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