Evidence map›Paper›PMID 40857666›Full record

ArticleBlood2025

A prime editing strategy to rewrite the γ-globin promoters and reactivate fetal hemoglobin for sickle cell disease.

Anne Chalumeau, Maria Bou Dames, Letizia Fontana, Simone Amistadi, Panagiotis Antoniou, Priyanka Loganathan, Margaux Mombled, Guillaume Corre, Martin Peterka, Mario Amendola and 4 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Blood, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

5 citing papers in PubMed.

  1. Review
  2. Article
  3. Review
  4. Review
  5. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

14 authors.

Anne ChalumeauUniversité Paris Cité, Imagine Institute, Laboratory of Chromatin and Gene Regulation during Development, INSERM Unité Mixte de Recherche 1163, Paris, France.
Maria Bou DamesUniversité Paris Cité, Imagine Institute, Laboratory of Chromatin and Gene Regulation during Development, INSERM Unité Mixte de Recherche 1163, Paris, France.ORCID 0009-0004-8325-8142
Letizia FontanaUniversité Paris Cité, Imagine Institute, Laboratory of Chromatin and Gene Regulation during Development, INSERM Unité Mixte de Recherche 1163, Paris, France.ORCID 0009-0001-8603-5188
Simone AmistadiUniversité Paris Cité, Imagine Institute, Laboratory of Chromatin and Gene Regulation during Development, INSERM Unité Mixte de Recherche 1163, Paris, France.ORCID 0000-0002-1140-9165
Panagiotis AntoniouGenome Engineering, Discovery Sciences, Research and Development, AstraZeneca, Gothenburg, Sweden.
Priyanka LoganathanUniversité Paris Cité, Imagine Institute, Laboratory of Chromatin and Gene Regulation during Development, INSERM Unité Mixte de Recherche 1163, Paris, France.
Margaux MombledGenethon, INSERM Unité Mixte de Recherche S951, Evry, France.
Guillaume CorreGenethon, INSERM Unité Mixte de Recherche S951, Evry, France.ORCID 0000-0002-0755-8336
Martin PeterkaGenome Engineering, Discovery Sciences, Research and Development, AstraZeneca, Gothenburg, Sweden.ORCID 0000-0002-1877-662X
Mario AmendolaGenethon, INSERM Unité Mixte de Recherche S951, Evry, France.ORCID 0000-0002-1188-8856
Carine GiovannangeliDépartement Adaptation du Vivant, Museum National d'Histoire Naturelle, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7196, INSERM Unité Mixte de Recherche 1154, Paris, France.
Marcello MarescaGenome Engineering, Discovery Sciences, Research and Development, AstraZeneca, Gothenburg, Sweden.
Annarita MiccioUniversité Paris Cité, Imagine Institute, Laboratory of Chromatin and Gene Regulation during Development, INSERM Unité Mixte de Recherche 1163, Paris, France.ORCID 0000-0002-3409-9665
Mégane BrussonUniversité Paris Cité, Imagine Institute, Laboratory of Chromatin and Gene Regulation during Development, INSERM Unité Mixte de Recherche 1163, Paris, France.ORCID 0000-0001-8567-444X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

abstractFetal hemoglobin reactivation is a promising therapy for β-hemoglobinopathies. We developed a prime editing strategy that introduces multiple mutations in the fetal γ-globin promoters that are expected to increase their activity. We tested multiple targets and optimized a variety of parameters to achieve ∼50% of precise edits in a hematopoietic cell line, with minimal off-target effects. This work improved our understanding of the complex DNA repair mechanisms involved in prime editing. We tested this strategy in patients' hematopoietic stem/progenitor cells. Although editing efficiency was variable among donors, erythroid clones carrying multiple mutations expressed a significantly higher γ-globin level than cells carrying individual mutations, confirming the potential therapeutic benefit of our combined strategy for patients with β-hemoglobinopathies.

Indexed as

Anemia, Sickle CellFetal Hemoglobingamma-GlobinsGene EditingPromoter Regions, GeneticHematopoietic Stem CellsHumansMutationFetal Hemoglobingamma-Globins

Identifiers

PMID40857666
PMCPMC12824697

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.