Modified lentiviral globin gene therapy for pediatric β 0 /β 0 transfusion-dependent β-thalassemia: A single-center, single-arm pilot trial.

β ⁰ /β ⁰ 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 interim analysis of a single-center, single-arm pilot trial (NCT05015920) evaluating the safety and efficacy of a β-globin expression-optimized and insulator-engineered lentivirus-modified cell product (BD211) in β ⁰ /β ⁰ TDT. Two female children were enrolled, infused with BD211, and followed up for an average of 25.5 months. Engraftment of genetically modified hematopoietic stem and progenitor cells was successful and sustained in both patients. No unexpected safety issues occurred during conditioning or after infusion. Both patients achieved transfusion independence for over 22 months. The treatment extended the lifespan of red blood cells by over 42 days. Single-cell DNA/RNA-sequencing analysis of the dynamic changes of gene-modified cells, transgene expression, and oncogene activation showed no notable adverse effects. Optimized lentiviral gene therapy may safely and effectively treat all β-thalassemia.
Competing Interests: Declaration of interests Y.C. is a co-founder and advisor of BDgene Therapeutics. S. Ling and X.W. filed two patents related to this work (“Lentiviral vector applicable to gene therapy of thalassemia and sickle anemia,” ZL201910824134.8, September 2, 2019, China; and “Lentiviral vector applicable to gene therapy of thalassemia and sickle anemia,” ZL202210013838.9, January 6, 2022, China).
(Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)