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Annual Review of Medicine

Volume 74, 2023

Diverse Approaches to Gene Therapy of Sickle Cell Disease

Abstract

Sickle cell disease (SCD) results from a single base pair change in the sixth codon of the β-globin chain of hemoglobin, which promotes aggregation of deoxyhemoglobin, increasing rigidity of red blood cells and causing vaso-occlusive and hemolytic complications. Allogeneic transplant of hematopoietic stem cells (HSCs) can eliminate SCD manifestations but is limited by absence of well-matched donors and immune complications. Gene therapy with transplantation of autologous HSCs that are gene-modified may provide similar benefits without the immune complications. Much progress has been made, and patients are realizing significant clinical improvements in multiple trials using different approaches with lentiviral vector–mediated gene addition to inhibit hemoglobin aggregation. Gene editing approaches are under development to provide additional therapeutic opportunities. Gene therapy for SCD has advanced from an attractive concept to clinical reality.

Keyword(s): CRISPR, gene editing, gene therapy, hematopoietic stem cell transplant, lentiviral vector, sickle cell disease
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/content/journals/10.1146/annurev-med-042921-021707
2023-01-27
2024-04-19
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Diverse Approaches to Gene Therapy of Sickle Cell Disease
Annual Review of Medicine 74, 473 (2023); https://doi.org/10.1146/annurev-med-042921-021707
/content/journals/10.1146/annurev-med-042921-021707
/content/journals/10.1146/annurev-med-042921-021707
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