ArticleMolecular therapy : the journal of the American Society of Gene Therapy2024
Safety and efficacy studies of CRISPR-Cas9 treatment of sickle cell disease highlights disease-specific responses.
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 16 papers.
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Who cites it
16 citing papers in PubMed.
- Enhanced γ-globin reactivation and sickle cell correction through a repressor-to-activator motif switch in theMolecular therapy. Nucleic acids · 2026Article
- On-target and off-target activities of CRISPR therapeutics across scales.Trends in biotechnology · 2026Review
- The future of pediatric gene therapy: CRISPR-Cas9, AI, and personalized medicine.Pediatric research · 2026Review
- Engraftment Outcome of CRISPR/Cas9-Edited Hematopoietic Stem Cells for Genetic Diseases: A Systematic Review and Meta-Analysis of Preclinical Evidence.Journal of hematology · 2026Article
- Emerging trends in gene and cell therapy: CRISPR in DNA editing and beyond.Cell reports. Medicine · 2026Review
- Engineering the auxin-inducible degron system for tunable in vivo control of organismal physiology.Nature communications · 2025Article
- Article
- Emerging Therapies for Sickle Cell Disease: From Symptom Management to Curative Gene Therapy.Cureus · 2025Review
- Genomic Editing of a Pathogenic Sequence Variant inCirculation · 2025Article
- Disrupting ZBTB7A or BCL11A binding sites reactivates fetal hemoglobin in erythroblasts from healthy and βScientific reports · 2025Article
- A differentiated β-globin gene replacement strategy uses heterologous introns to restore physiological expression.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Harnessing bacterial immunity: CRISPR-Cas system as a versatile tool in combating pathogens and revolutionizing medicine.Frontiers in cellular and infection microbiology · 2025Review
- Emerging Gene Therapies in Sickle Cell Disease: A Comparative Review of Efficacy and Safety Against Standard Treatments.Journal of blood medicine · 2025Review
- Development of artificial transcription factors and their applications in cell reprograming, genetic screen, and disease treatment.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Review
- Gene editing efficiencies and hematopoietic stem cell fitness in sickle cell disease: A balancing act.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Gene Therapy for Inherited Liver Disease: To Add or to Edit.International journal of molecular sciences · 2024Review
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12 authors.
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Abstract
Fetal hemoglobin (HbF) reactivation expression through CRISPR-Cas9 is a promising strategy for the treatment of sickle cell disease (SCD). Here, we describe a genome editing strategy leading to reactivation of HbF expression by targeting the binding sites (BSs) for the lymphoma-related factor (LRF) repressor in the γ-globin promoters. CRISPR-Cas9 treatment in healthy donor (HD) and patient-derived HSPCs resulted in a high frequency of LRF BS disruption and potent HbF synthesis in their erythroid progeny. LRF BS disruption did not impair HSPC engraftment and differentiation but was more efficient in SCD than in HD cells. However, SCD HSPCs showed a reduced engraftment and a myeloid bias compared with HD cells. We detected off-target activity and chromosomal rearrangements, particularly in SCD samples (likely because of the higher overall editing efficiency) but did not impact the target gene expression and HSPC engraftment and differentiation. Transcriptomic analyses showed that the editing procedure results in the up-regulation of genes involved in DNA damage and inflammatory responses, which was more evident in SCD HSPCs. This study provides evidence of efficacy and safety for an editing strategy based on HbF reactivation and highlights the need of performing safety studies in clinically relevant conditions, i.e., in patient-derived HSPCs.
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