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Lentiviral Vectors for Hematopoietic Stem Cell Gene Therapy Restore α-Globin Expression in α-Thalassemia Red Blood Cells

GSE292575 Homo sapiens Expression profiling by high throughput sequencing 5 samples Submitted 2025/07/10 Platform GPL34284
Summary
Alpha thalassemia major (ATM) is an inherited blood disorder caused by the absence of all four α-globin genes (HBA2/1), resulting in severe anemia and lifelong transfusion dependence. While allogeneic hematopoietic stem cell transplant (HSCT) offers a potential cure, donor availability remains limited. We present a gene therapy approach for autologous HSCT, using lentiviral vectors (LVs) to deliver HBA2 under the regulation of optimized β-globin locus control region (LCR) enhancers, restoring α-globin expression. The best-performing LVs, EV-α and EV-α-UV, achieved 90-100% transduction efficiency in human hematopoietic stem and progenitor cells (HSPCs), optimal vector copy numbers, and a safe integration profile. ATM-derived HSPCs from three donors treated with these LVs yielded α/β-globin mRNA and chain ratios within the therapeutic range (~0.5+), and restored hemoglobin levels by 50 to 100%. These findings establish the safety and clinical potential of EV-α and EV-α-UV as a promising autologous stem cell gene therapy for ATM.
Published in
Lentiviral vectors for hematopoietic stem cell gene therapy restore α-globin expression in α-thalassemia red blood cells
Segura EER, Hart K, Campo Fernandez B et al. · Cell reports. Medicine 2025 · PMID 40967220 · doi:10.1016/j.xcrm.2025.102362
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Also filed as BioProject PRJNA1240240 and SRA study SRP572226. Searching any of these in the dataset finder brings you back here.

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