Department of Pediatrics, Division of Hematology/Oncology, David Geffen School of Medicine, University of California, Los Angeles, USA; email:
Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, USA.
Annu Rev Med. 2023 Jan 27;74:473-487. doi: 10.1146/annurev-med-042921-021707. Epub 2022 Sep 6.
Sickle cell disease (SCD) results from a single base pair change in the sixth codon of the β-globin chain of hemoglobin, which promotes aggregation of deoxyhemoglobin, increasing rigidity of red blood cells and causing vaso-occlusive and hemolytic complications. Allogeneic transplant of hematopoietic stem cells (HSCs) can eliminate SCD manifestations but is limited by absence of well-matched donors and immune complications. Gene therapy with transplantation of autologous HSCs that are gene-modified may provide similar benefits without the immune complications. Much progress has been made, and patients are realizing significant clinical improvements in multiple trials using different approaches with lentiviral vector-mediated gene addition to inhibit hemoglobin aggregation. Gene editing approaches are under development to provide additional therapeutic opportunities. Gene therapy for SCD has advanced from an attractive concept to clinical reality.
镰状细胞病（SCD）是由于血红蛋白β 珠蛋白链第六位密码子的单个碱基对改变，促进脱氧血红蛋白聚集，增加红细胞刚性，导致血管阻塞和溶血性并发症。同种异体造血干细胞（HSCs）移植可以消除 SCD 表现，但由于缺乏匹配良好的供体和免疫并发症而受到限制。通过移植经基因修饰的自体 HSCs 进行基因治疗可能会提供类似的益处，而没有免疫并发症。已经取得了很大进展，并且在使用不同方法的多项试验中，患者正在使用慢病毒载体介导的基因添加来抑制血红蛋白聚集，从而实现了显著的临床改善。基因编辑方法正在开发中，以提供更多的治疗机会。SCD 的基因治疗已经从一个有吸引力的概念发展到临床现实。
