Sickle cell disease (SCD) is one of the most common single-gene genetic diseases in the world, with high morbidity, high disability, and significant geographic and racial clustering. Currently, clinical treatment is based on symptomatic relief, and the traditional drug hydroxyurea (HU) improves the condition by elevating fetal hemoglobin (HbF), but there are long-term toxicity and efficacy limitations. This paper systematically comprehends the therapeutic progress of SCD through literature review, focusing on the core strategies and research breakthroughs of gene editing technology. Studies have shown that the CRISPR/Cas9 system has realized the synergistic effect of pathogenic mutation correction and HbF induction in human cell models, which provides a new pathway for the eradication of SCD. However, the clinical translation of gene editing technology faces multiple challenges, including the off-target effect of CRISPR/Cas9, the insufficient editing efficiency of hematopoietic stem cells, the optimization of the safety of the delivery system, the development of novel mobilizing agents such as Plexafoc and chemically modified mRNA vectors, as well as the integration of new and emerging technologies, such as single-cell transcriptome sequencing.
Xinhong ZHANG (Tue,) studied this question.