上海交通大学蔡宇伽等研究人员合作完成，改良慢病毒球蛋白基因疗法治疗小儿β⁰/β⁰输血依赖型β地中海贫血症的临床试验。相关论文于2024年5月16日在线发表在《细胞—干细胞》杂志上。

据介绍，β⁰/β⁰地中海贫血症是TDT中最严重的类型，目前仍是慢病毒基因疗法面临的挑战。

附：英文原文

Title: Modified lentiviral globin gene therapy for pediatric β0/β0 transfusion-dependent β-thalassemia: A single-center, single-arm pilot trial

Author: Shiqi Li, Sikai Ling, Dawei Wang, Xiaoyuan Wang, Fangyuan Hao, Liufan Yin, Zhongtao Yuan, Lin Liu, Lin Zhang, Yu Li, Yingnian Chen, Le Luo, Ying Dai, Lihua Zhang, Lvzhe Chen, Dongjie Deng, Wei Tang, Sujiang Zhang, Sanbin Wang, Yujia Cai

Issue&Volume: 2024-05-16

Abstract: β0/β0 thalassemia is the most severe type of transfusion-dependent β-thalassemia (TDT)and is still a challenge facing lentiviral gene therapy. Here, we report the interimanalysis of a single-center, single-arm pilot trial (NCT05015920) evaluating the safetyand efficacy of a β-globin expression-optimized and insulator-engineered lentivirus-modifiedcell product (BD211) in β0/β0 TDT. Two female children were enrolled, infused with BD211, and followed up for anaverage of 25.5 months. Engraftment of genetically modified hematopoietic stem andprogenitor cells was successful and sustained in both patients. No unexpected safetyissues occurred during conditioning or after infusion. Both patients achieved transfusionindependence for over 22 months. The treatment extended the lifespan of red bloodcells by over 42 days. Single-cell DNA/RNA-sequencing analysis of the dynamic changesof gene-modified cells, transgene expression, and oncogene activation showed no notableadverse effects. Optimized lentiviral gene therapy may safely and effectively treatall β-thalassemia.

DOI: 10.1016/j.stem.2024.04.021

Source: https://www.cell.com/cell-stem-cell/abstract/S1934-5909(24)00175-9