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December 8, 2025BloodOpen Access

A genome-wide CRISPR activation screen identifies novel γ-globin regulators

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Authors

CMCarea MullinGMGreggory MyersZLZesen Lin

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Overview

A genome-wide screen reveals novel lentiviral activation strategies to enhance γ-globin expression in erythroid cells.

Key Points

  • The study aims to identify novel regulators of γ-globin expression to explore therapeutic avenues for β-hemoglobinopathies.
  • Conducted a genome-wide pooled CRISPR activation screen using HUDEP-2 cells.
  • Transduced cells with lentiviral sgRNA libraries to identify γ-globin regulators.
  • Analyzed γ-globin expression via HbF staining and deep sequencing of sgRNAs.
  • Identified novel γ-globin activators including HIC1, CHCHD7, FXR2, ANKH, and SKIL.
  • Activation of target genes resulted in over 2-fold increase in γ-globin mRNA levels and %F-Cells.
  • Results in primary human hematopoietic stem and progenitor cells validated the findings.

Cite This Study

Mullin et al. (2025) studied this question.

synapsesocial.com/papers/69362f364fa91c937236d2f9https://doi.org/10.1182/blood-2025-1136
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