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December 8, 2025Blood

Targeted disruption of BCL11A ZnF4 enhances fetal hemoglobin in β-thalassemia and sickle cell disease: A druggable approach

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Authors

SFSafana FarooqALAlshad S. LalaniOOOliver G. Ottmann

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Overview

CRISPR-Cas9 gene editing enhances fetal hemoglobin in β-thalassemia and sickle cell disease, suggesting a novel treatment approach.

Key Points

  • This study aims to investigate the role of BCL11A ZnF4 in gene silencing and to evaluate its disruption for HbF induction in β-thalassemia and sickle cell disease.
  • Targeted disruption of BCL11A ZnF4 using CRISPR-Cas9 in patient-derived hematopoietic stem/progenitor cells.
  • Developed induced pluripotent stem cell models for common β-globin mutations.
  • Evaluated the effects of gene editing on fetal hemoglobin expression and cell differentiation.
  • Designed a targeted delivery system for gene-editing components using liposomal and exosomal vectors.
  • CRISPR-Cas9 editing led to a significant increase in fetal hemoglobin expression (p < 0.001).
  • Edited cells maintained multilineage differentiation and showed increased γ-globin expression.
  • In vivo studies in humanized mouse models confirmed elevated fetal hemoglobin levels post-editing.
  • The targeted delivery system effectively delivered gene-editing components with minimal off-target effects.

Cite This Study

Farooq et al. (2025) studied this question.

synapsesocial.com/papers/69362f6e4fa91c937236e145https://doi.org/10.1182/blood-2025-6099
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1CRISPR-directed epigenetic reprogramming of the FLT1 locus: a novel strategy for reversing fetal hemoglobin silencing in β-thalassemia minor2026
  2. 2Development and IND-enabling studies of a novel Cas9 genome-edited autologous CD34<sup>+</sup>cell therapy to induce fetal hemoglobin for sickle cell disease2024
  3. 3Multiplex CRISPR/Cas9 genome editing in hematopoietic stem cells for fetal hemoglobin reinduction generates chromosomal translocations2021 · 51 citations
  4. 4Development and IND-enabling studies of a novel Cas9 genome-edited autologous CD34+ cell therapy to induce fetal hemoglobin for sickle cell disease2024 · 17 citations
  5. 5Silencing of BCL11A by disrupting enhancer-dependent epigenetic insulation2025 · 1 citations