Abstract：
Gene therapy has shown significant potential in treating various diseases, particularly inherited blood disorders such as hemophilia, sickle cell disease, and thalassemia. Advances in understanding the regulatory network of disease-associated genes have led to the identification of additional therapeutic targets for treatment, especially for β-hemoglobinopathies. Erythroid regulatory factor BCL11A offers the most promising therapeutic target for β-hemoglobinopathies and reduction of its expression using the commercialized gene therapy product Casgevy was approved for use in the UK and USA in 2023. Notably, the emergence of innovative gene editing technologies has further broadened the gene therapy landscape, presenting new possibilities for treatment. Intensive studies indicate that base editing and prime editing, built upon CRISPR technology, enable precise single-base modification in hematopoietic stem cells for addressing inherited blood disorders ex vivo and in vivo. In this review, we present an overview of the current landscape of gene therapies, focusing on clinical research and gene therapy products for inherited blood disorders, evaluation of potential gene targets, and the gene editing tools employed in current gene therapy practices, which provides an insight for the establishment of safer and more effective gene therapy methods for a wider range of diseases in the future.
摘要：
基因治疗在治疗各种疾病方面显示出巨大的潜力，特别是遗传性血液疾病，如血友病，镰状细胞病,和地中海贫血。在理解疾病相关基因的调控网络方面的进展已经导致了对其他治疗靶点的识别。尤其是β-血红蛋白病。红系调节因子BCL11A为β-血红蛋白病提供了最有希望的治疗靶标，并且使用商业化的基因治疗产品Casgevy在2023年被批准在英国和美国使用。值得注意的是,创新基因编辑技术的出现进一步拓宽了基因治疗领域，为治疗提供新的可能性。深入研究表明，基础编辑和主要编辑，基于CRISPR技术，能够在造血干细胞中进行精确的单碱基修饰，以解决离体和体内遗传性血液疾病。在这次审查中,我们概述了基因疗法的现状，专注于遗传性血液疾病的临床研究和基因治疗产品，潜在基因靶标的评估，以及目前基因治疗实践中使用的基因编辑工具，这为未来针对更广泛的疾病建立更安全、更有效的基因治疗方法提供了启示。
