近日，上海科技大学陈佳团队提出了碱基编辑治疗β-地中海贫血的临床应用。2026年4月8日出版的《自然》发表了这项成果。

在此之前，该课题组研究人员采用实验室规模的电穿孔技术，使用变压器碱基编辑器对来自β-地中海贫血患者的CD34⁺造血干细胞和祖细胞进行了编辑，目的是靶向HBG1和HBG2启动子中转录抑制因子BCL11A的结合基序，从而重新激活胎儿血红蛋白（HbF）的生成。

这里研究人员给出一个阶段的结果1项临床试验（ClinicalTrials.gov标识符：NCT06024876）， 该试验共纳入5例患者，这些患者接受了采用临床规模变压器碱基编辑器修饰的自体CD34⁺细胞（CS-101）。中位随访时间为CS-101输注后23.0个月，中性粒细胞和血小板植入的中位时间分别为16天和25天。

此外，所有患者都停止了红细胞输注，自CS-101输注后至末次输血的中位时间为18天。输注后第3个月，平均总血红蛋白浓度为12.4±1.0 g/dl，平均HbF浓度为11.5±0.9 g/dl^-1；在整个随访期间，这些水平保持在相似或更高的水平，这表明造血系统正在快速重建。CS-101的不良事件与多番清髓调节和自体造血干细胞和祖细胞移植的不良事件基本一致。没有死亡或癌症病例的报告。总之，CS-101可导致总血红蛋白和HbF水平的快速和持续增加，从而导致早期和持久的输血独立性。

据介绍，β-地中海贫血是由β-血红蛋白的产生减少或缺失引起的。

附：英文原文

Title: Clinical application of base editing for treating β-thalassaemia

Author: Lai, Yongrong, Liu, Rongrong, Wang, Lijie, Ma, Xu-Kai, Li, Yaliang, Yang, Gaohui, Shi, Lingling, Guo, Yi-Lin, Wei, Zhenbin, Zhou, Xuemei, Xu, Wenchao, Hou, Yaofeng, Miccio, Annarita, Yang, Bei, Mou, Xiaodun, Yang, Li, Chen, Jia

Issue&Volume: 2026-04-08

Abstract: β-Thalassaemia is caused by reduced or absent production of β-haemoglobin1,2,3,4. Previously, we performed laboratory-scale electroporation of CD34+ haematopoietic stem and progenitor cells from patients with β-thalassaemia using a transformer base editor5,6. The aim was to target the binding motif of the transcription repressor BCL11A in the HBG1 and HBG2 promoters7 to reactivate fetal haemoglobin (HbF) production. Here we present results of a phase1 clinical trial (ClinicalTrials.gov identifier: NCT06024876) of five patients who received autologous CD34+ cells modified using a transformer base editor at clinical scale (CS-101). With a median follow-up of 23.0months after CS-101 infusion, the median times to neutrophil and platelet engraftment were 16days and 25days, respectively. Moreover, all patients had stopped red blood cell transfusions, with a median time to the last transfusion of 18days after CS-101 infusion. The mean total haemoglobin and HbF concentrations were 12.4±1.0 and 11.5±0.9gdl–1, respectively, at month3 after infusion. These levels remained at similar or higher levels throughout the follow-up period, which indicated rapid haematopoietic reconstitution. The adverse events of CS-101 were generally consistent with those of busulfan myeloablative conditioning and autologous haematopoietic stem and progenitor cell transplantation. No deaths or cancer occurrences were reported. In summary, CS-101 can lead to rapid and sustained increases in both total haemoglobin and HbF levels, which resulted in early and enduring transfusion independence.

DOI: 10.1038/s41586-026-10342-9

Source: https://www.nature.com/articles/s41586-026-10342-9