Research ArticleGene Therapy

Sustained fetal hemoglobin induction in vivo is achieved by BCL11A interference and coexpressed truncated erythropoietin receptor

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Science Translational Medicine  28 Apr 2021:
Vol. 13, Issue 591, eabb0411
DOI: 10.1126/scitranslmed.abb0411

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Improved gene therapy for SCD

Sickle cell disease (SCD) leads to substantial morbidity and decreased life span. It has been proven difficult to achieve therapeutic γ-globin production using hematopoietic stem cell gene therapy. Uchida et al. addressed this by developing a truncated human erythropoietin receptor to increase erythroid cell proliferation and differentiation. They added a microRNA-adapted short hairpin RNA interfering with the gene BCL11A (shmiR BCL11A) to increase γ-globin concentrations. A lentiviral vector encoding shmiR BCL11A and the truncated erythropoietin receptor was injected into CD34+ cells of macaques and autologously transplanted, leading to increased erythroid cells producing γ-globin at therapeutic levels. This promising approach may lead to improved gene therapy for SCD.

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