ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
Introducing a hemoglobin G-Makassar variant in HSCs by in vivo base editing treats sickle cell disease in mice.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Article
- Base editing for precision therapeutics.Cell genomics · 2026Review
- Mechanistic machine learning for prediction of prime editing outcomes.Nature biotechnology · 2026Article
- DNA and RNA editing for the therapy of human diseases: current status, challenges, and future prospects.Molecular biomedicine · 2026Review
- Exploring Affordable Curative Therapy for Sickle Cell Disease in Africa: A Comprehensive Overview.American journal of hematology · 2026Review
- Mechanistic machine learning enables interpretable and generalizable prediction of prime editing outcomes.bioRxiv : the preprint server for biology · 2026Article
- From Bench to Bedside: Ethical and Clinical Best Practices for Genome Editing Applications.International journal of molecular sciences · 2026Review
- Gene Therapy of Beta Hemoglobinopathies.Biomedicines · 2025Review
- Review
- Emerging Therapies for Sickle Cell Disease: From Symptom Management to Curative Gene Therapy.Cureus · 2025Review
- Hematopoietic stem cell therapy with gene modification to treat sickle cell disease.Stem cells translational medicine · 2025Review
- Review
- Engraftment and persistence ofScience translational medicine · 2025Article
- Genome editing strategies for targeted correction of β-globin mutation in sickle cell disease: From bench to bedside.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Current and future treatments for sickle cell disease: From hematopoietic stem cell transplantation to in vivo gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- THERAPIES FOR NEONATAL DISEASES OF THE SURFACTANT SYSTEM.Transactions of the American Clinical and Climatological Association · 2025Review
- Improving efficacy of in vivo therapy of sickle cell disease by hijacking natural biology of hematopoietic stem cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
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Authors and funding
13 authors.
Funding
Abstract
Precise repair of the pathogenic mutation in hematopoietic stem cells (HSCs) represents an ideal cure for patients with sickle cell disease (SCD). Here, we demonstrate correction of the SCD phenotype by converting the sickle mutation codon (GTG) into a benign G-Makassar variant (GCG) using in vivo base editing in HSCs. We show successful production of helper-dependent adenoviral vectors expressing an all-in-one base editor mapping to the sickle mutation site. In HSC-enriched cells from SCD patients, transduction with the base editing vector in vitro resulted in 35% GTG > GCG conversion and phenotypic improvements in the derived red blood cells. After ex vivo transduction of HSCs from an SCD mouse model and subsequent transplantation, we achieved an average of 88% editing at the target site in transplanted mice. Importantly, in vivo HSC base editing followed by selection generated 24.5% Makassar variant in long-term repopulating HSCs of SCD mice. The treated animals demonstrated correction of disease hallmarks without any noticeable side effects. Off-target analyses at top-scored genomic sites revealed no off-target editing. This in vivo approach requires a single non-integrating vector, only intravenous/subcutaneous injections, and minimal in vivo selection. This technically simple approach holds potential for scalable applications in resource-limiting regions where SCD is prevalent.
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