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Annual Review of Pharmacology and Toxicology

Volume 65, 2025

Treating Sickle Cell Disease: Gene Therapy Approaches

Abstract

Sickle cell disease (SCD) is a hereditary blood disorder characterized by the presence of abnormal hemoglobin molecules and thus distortion (sickling) of the red blood cells. SCD causes chronic pain and organ damage and shortens life expectancy. Gene therapy emerges as a potentially curative approach for people with SCD who lack a matched sibling donor for hematopoietic stem cell transplantation. Here, we review recent progress in gene therapy for SCD and focus on innovative technologies that target the genetic roots of the disease. We also review the challenges associated with gene therapy, including oncogenic risks, and the need for refined delivery methods. Despite these hurdles, the rapidly evolving landscape of gene therapy for SCD raises hope for a paradigm shift in the treatment of this debilitating disease. As research progresses, a deeper understanding of the molecular mechanisms involved and continuous improvements in gene-editing technologies promise to bring gene therapy for SCD closer to mainstream clinical application, offering a transformative, curative option for patients with this genetic disorder.

Keyword(s): gene addition, gene editing, gene therapy, genotoxicity, sickle cell disease
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/content/journals/10.1146/annurev-pharmtox-022124-022000
2025-01-23
2025-04-23
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/content/journals/10.1146/annurev-pharmtox-022124-022000
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Treating Sickle Cell Disease: Gene Therapy Approaches
Annual Review of Pharmacology and Toxicology 65, 397 (2025); https://doi.org/10.1146/annurev-pharmtox-022124-022000
/content/journals/10.1146/annurev-pharmtox-022124-022000
/content/journals/10.1146/annurev-pharmtox-022124-022000
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