ArticleExperimental hematology2015
Potentially therapeutic levels of anti-sickling globin gene expression following lentivirus-mediated gene transfer in sickle cell disease bone marrow CD34+ cells.
Article in Experimental hematology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 34 citations in OpenAlex.
- Clinical outcomes of lentiviral vector gene therapy for sickle cell disease.Blood advances · 2026Trial
- The Optimized γ-Globin Lentiviral Vector GGHI-mB-3D Leads to Nearly Therapeutic HbF Levels In Vitro in CD34Viruses · 2022Article
- Elevated neuregulin-1Endocrine and metabolic science · 2021Article
- Development of β-globin gene correction in human hematopoietic stem cells as a potential durable treatment for sickle cell disease.Science translational medicine · 2021Article
- CRISPR/Cas9 gene editing for curing sickle cell disease.Transfusion and apheresis science : official journal of the World Apheresis Association : official journal of the European Society for Haemapheresis · 2021Review
- The mRNA-Binding Protein IGF2BP1 Restores Fetal Hemoglobin in Cultured Erythroid Cells from Patients with β-Hemoglobin Disorders.Molecular therapy. Methods & clinical development · 2020Article
- High level of fetal-globin reactivation by designed transcriptional activator-like effector.Blood advances · 2020Article
- Highly efficient editing of the β-globin gene in patient-derived hematopoietic stem and progenitor cells to treat sickle cell disease.Nucleic acids research · 2019Article
- Gene Therapy for Beta-Hemoglobinopathies: Milestones, New Therapies and Challenges.Molecular diagnosis & therapy · 2019Review
- Pre-clinical Development of a Lentiviral Vector Expressing the Anti-sickling βAS3 Globin for Gene Therapy for Sickle Cell Disease.Molecular therapy. Methods & clinical development · 2018Article
- Gene Therapy for Hemoglobinopathies.Human gene therapy · 2018Review
- Integrating HDAd5/35++ Vectors as a New Platform for HSC Gene Therapy of Hemoglobinopathies.Molecular therapy. Methods & clinical development · 2018Article
- Fetal haemoglobin induction in sickle cell disease.British journal of haematology · 2018Review
- Sickle cells produce functional immune modulators and cytotoxics.American journal of hematology · 2017Article
- Bone Marrow as a Hematopoietic Stem Cell Source for Gene Therapy in Sickle Cell Disease: Evidence from Rhesus and SCD Patients.Human gene therapy. Clinical development · 2017Article
- The potential of gene therapy approaches for the treatment of hemoglobinopathies: achievements and challenges.Therapeutic advances in hematology · 2016Review
- Gene Insertion Into Genomic Safe Harbors for Human Gene Therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Review
- Genetic treatment of a molecular disorder: gene therapy approaches to sickle cell disease.Blood · 2016Review
- 2015 Clinical trials update in sickle cell anemia.American journal of hematology · 2015Review
- Amelioration of murine sickle cell disease by nonablative conditioning and γ-globin gene-corrected bone marrow cells.Molecular therapy. Methods & clinical development · 2015Article
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Sickle cell disease (SCD) can be cured by allogeneic hematopoietic stem cell transplant. However, this is only possible when a matched donor is available, making the development of gene therapy using autologous hematopoietic stem cells a highly desirable alternative. We used a culture model of human erythropoiesis to directly compare two insulated, self-inactivating, and erythroid-specific lentiviral vectors, encoding for γ-globin (V5m3-400) or a modified β-globin (βAS3-FB) for production of antisickling hemoglobin (Hb) and correction of red cell deformability after deoxygenation. Bone marrow CD34+ cells from three SCD patients were transduced using V5m3-400 or βAS3-FB and compared with mock-transduced SCD or healthy donor CD34+ cells. Lentiviral transduction did not impair cell growth or differentiation, as gauged by proliferation and acquisition of erythroid markers. Vector copy number averaged approximately one copy per cell, and corrective globin mRNA levels were increased more than sevenfold over mock-transduced controls. Erythroblasts derived from healthy donor and mock-transduced SCD cells produced a low level of fetal Hb that was increased to 23.6 ± 4.1% per vector copy for cells transduced with V5m3-400. Equivalent levels of modified normal adult Hb of 17.6 ± 3.8% per vector copy were detected for SCD cells transduced with βAS3-FB. These levels of antisickling Hb production were sufficient to reduce sickling of terminal-stage red blood cells upon deoxygenation. We concluded that the achieved levels of fetal Hb and modified normal adult Hb would likely prove therapeutic to SCD patients who lack matched donors.
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