PDF(Pubmed)
Abstract：
Lessons learned from decades-long practice in the transplantation of hematopoietic stem and progenitor cells (HSPCs) to treat severe inherited disorders or cancer, have set the stage for the current ex vivo gene therapies using autologous gene-modified hematopoietic stem and progenitor cells that have treated so far, hundreds of patients with monogenic disorders. With increased knowledge of hematopoietic stem and progenitor cell biology, improved modalities for patient conditioning and with the emergence of new gene editing technologies, a new era of hematopoietic stem and progenitor cell-based gene therapies is poised to emerge. Gene editing has the potential to restore physiological expression of a mutated gene, or to insert a functional gene in a precise locus with reduced off-target activity and toxicity. Advances in patient conditioning has reduced treatment toxicities and may improve the engraftment of gene-modified cells and specific progeny. Thanks to these improvements, new potential treatments of various blood- or immune disorders as well as other inherited diseases will continue to emerge. In the present review, the most recent advances in hematopoietic stem and progenitor cell gene editing will be reported, with a focus on how this approach could be a promising solution to treat non-blood-related inherited disorders and the mechanisms behind the therapeutic actions discussed.
摘要：
从几十年来移植造血干细胞和祖细胞（HSPCs）治疗严重遗传性疾病或癌症的实践中吸取的经验教训，已经为目前使用自体基因修饰的造血干细胞和祖细胞的离体基因治疗奠定了基础，数百名单基因疾病患者。随着造血干细胞和祖细胞生物学知识的增加，改进了患者调理的方式，并随着新基因编辑技术的出现，基于造血干细胞和祖细胞的基因治疗的新时代即将出现。基因编辑有可能恢复突变基因的生理表达，或将功能基因插入到具有降低的脱靶活性和毒性的精确基因座中。患者调理的进展降低了治疗毒性，并可能改善基因修饰细胞和特定后代的植入。由于这些改进，各种血液或免疫疾病以及其他遗传性疾病的新的潜在治疗方法将继续出现。在本次审查中，造血干细胞和祖细胞基因编辑的最新进展将被报道，重点是这种方法如何成为治疗非血液相关遗传性疾病的有希望的解决方案，以及所讨论的治疗措施背后的机制。
