2025-09-17 カリフォルニア大学ロサンゼルス校(UCLA)
<関連情報>
- https://newsroom.ucla.edu/releases/stem-cell-gene-therapy-blood-disorder-alpha-thalassemia-major-ucla
- https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00435-5
造血幹細胞遺伝子治療用レンチウイルスベクターがα-サラセミア赤血球におけるα-グロビン発現を回復 Lentiviral vectors for hematopoietic stem cell gene therapy restore α-globin expression in α-thalassemia red blood cells
Eva E.R. Segura ∙ Kevyn Hart ∙ Beatriz Campo Fernandez ∙ … ∙ Frederic Bushman ∙ Tippi C. MacKenzie ∙ Donald B. Kohn
Cell Reports Medicine Published:September 17, 2025
DOI:https://doi.org/10.1016/j.xcrm.2025.102362
Graphical abstract
Highlights
- β-globin regulatory elements drive the α-globin gene
- Vector restores α-globin expression in alpha thalassemia patient red blood cells
- Rebalance of α/β-globin ratio and functional hemoglobin production
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 transplantation (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 in red blood cells. The best-performing LVs, erythroid vector-alpha (EV-α) and EV-α-UV, achieved up to 100% transduction efficiency in human hematopoietic stem and progenitor cells (HSPCs), optimal vector copy numbers, and safe integration profiles. 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%–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.
