The Application of CRISPR-Cas۹ in Sickle Cell Disease Treatment: From Molecular Mechanisms to Clinical and Ethical Challenges

Sickle cell disease (SCD) is a non-inherited disease caused by a point mutation of the -globin gene (HBB), resulting in abnormal hemoglobin S production (HbS). The CRISPR-Cas۹ system has been developed as an innovative tool for precise genome editing and offers potential therapeutic strategies for SCA. This technology allows targeted correction of the HBB mutation or the induction of fetal hemoglobin (HbF) to compensate for the failure of the HbS. Recent studies have shown that CRISPR-Cas۹ can efficiently edit the hematopoietic stem cells (HSCs) to restore normal -globin expression or to disrupt HbF suppressors such as BCL۱۱A. Preclinical studies have shown promising results, with the HSC successfully engrafted and producing healthy red cells in animal models. Furthermore, CRISPR-based ex vivo therapies reduce risks beyond target compared to in vitro approaches. Despite challenges such as delivery efficiency and long-term safety, clinical advances (such as ongoing CRISPR-SCA studies) highlight its transformative potential. This review discusses the molecular mechanisms of CRISPR-Cas۹ in SCA therapy, current research progress and future directions to translate this technology into therapeutic therapies.

کلیدواژه ها:

CRISPR-Cas۹ ، Sickle Cell Anemia ، Fetal Hemoglobin (HbF) ، BCL۱۱A ، Gene Editing