Gene transfer to and correction of hematopoietic stem cells (HSCs) are ideal strategies to cure a number of congenital and acquired disorders. However, transgene products may trigger immunological rejection of modified cells, limiting their therapeutic benefits. Preclinical and clinical data indicate that myeloablative total body irradiation (TBI) allows for efficient engraftment and tolerance to gene-modified HSCs. In contrast, myeloablative chemotherapy using busulfan or similar agents is only sufficient to induce tolerance to gene-modified HSCs producing no or non-immunogenic protein. If cells are modified to produce a protein that is xenogenic or congenitally absent in the patient, additional immunosuppression may be required to prevent an immunological reaction to the transduced cells. New gene editing and in vivo gene therapy techniques could pose additional immune concerns compared to ex vivo gene therapy methods. This review is intended to guide the design of conditioning and immunosuppression therapy in HSC-targeted gene therapy, as well as gene editing.

基因转移到造血干细胞（HSC）并进行修正是治疗许多先天性和后天性疾病的理想策略。然而，转基因产品可能会引发修饰细胞的免疫排斥反应，从而限制其治疗效果。临床前和临床数据表明，清髓性全身照射 (TBI) 可以实现基因修饰 HSC 的有效植入和耐受。相比之下，使用白消安或类似药物的清髓性化疗仅足以诱导对不产生或不产生免疫原性蛋白质的基因修饰HSC的耐受性。如果细胞被修饰以产生异种或患者体内先天性缺失的蛋白质，则可能需要额外的免疫抑制以防止对转导细胞的免疫反应。与离体基因治疗方法相比，新的基因编辑和体内基因治疗技术可能会引起额外的免疫问题。本综述旨在指导 HSC 靶向基因治疗以及基因编辑中调理和免疫抑制治疗的设计。