CRISPR Gene Therapy: A Promising One-Time Therapeutic Approach for Transfusion-Dependent β-Thalassemia—CRISPR-Cas9 Gene Editing for β-Thalassemia

Abstract

β-Thalassemia is an inherited hematological disorder that results from genetic changes in the β-globin gene, leading to the reduced or absent synthesis of β-globin. For several decades, the only curative treatment option for β-thalassemia has been allogeneic hematopoietic cell transplantation (allo-HCT). Nonetheless, rapid progress in genome modification technologies holds great potential for treating this disease and will soon change the current standard of care for β-thalassemia. For instance, the emergence of the CRISPR/Cas9 genome editing platform has opened the door for precision gene editing and can serve as an effective molecular treatment for a multitude of genetic diseases. Investigational studies were carried out to treat β-thalassemia patients utilizing CRISPR-based CTX001 therapy targeting the fetal hemoglobin silencer BCL11A to restore γ-globin expression in place of deficient β-globin. The results of recently carried out clinical trials provide hope of CTX001 being a promising one-time therapeutic option to treat β-hemoglobinopathies. This review provides an insight into the key scientific steps that led to the development and application of novel CRISPR/Cas9–based gene therapies as a promising therapeutic platform for transfusion-dependent β-thalassemia (TDT). Despite the resulting ethical, moral, and social challenges, CRISPR provides an excellent treatment option against hemoglobin-associated genetic diseases.

Keywords

• β-thalassemia
• β-globin
• γ-globin
• BCL11A
• CRISPR/Cas9 technology
• CTX001 therapy