Editing a γ-globin repressor binding site restores fetal hemoglobin synthesis and corrects the sickle cell disease phenotype

Author:

Weber Leslie123ORCID,Frati Giacomo34,Felix Tristan34ORCID,Hardouin Giulia34,Casini Antonio5ORCID,Wollenschlaeger Clara34ORCID,Meneghini Vasco34,Masson Cecile6,De Cian Anne7ORCID,Chalumeau Anne134,Mavilio Fulvio89ORCID,Amendola Mario10ORCID,Andre-Schmutz Isabelle14,Cereseto Anna5ORCID,El Nemer Wassim111213ORCID,Concordet Jean-Paul7,Giovannangeli Carine7,Cavazzana Marina1414ORCID,Miccio Annarita34ORCID

Affiliation:

1. Laboratory of Human Lymphohematopoiesis, INSERM UMR1163, Paris, France.

2. Paris Diderot University–Sorbonne Paris Cité, Paris, France.

3. Laboratory of chromatin and gene regulation during development, INSERM UMR1163, Paris, France.

4. Paris Descartes–Sorbonne Paris Cité University, Imagine Institute, Paris, France.

5. CIBIO, University of Trento, Trento, Italy.

6. Paris-Descartes Bioinformatics Platform, Imagine Institute, Paris 75015, France.

7. INSERM U1154, CNRS UMR7196, Museum National d’Histoire Naturelle, Paris, France.

8. Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.

9. Audentes Therapeutics, San Francisco, CA, USA.

10. Genethon, INSERM UMR951, Evry, France.

11. Biologie Intégrée du Globule Rouge UMR_S1134, Inserm, Univ. Paris Diderot, Sorbonne Paris Cité, Univ. de la Réunion, Univ. des Antilles, Paris, France.

12. Institut National de la Transfusion Sanguine, F-75015 Paris, France.

13. Laboratoire d’Excellence GR-Ex, Paris, France.

14. Biotherapy Department, Necker Children’s Hospital, Assistance Publique–Hôpitaux de Paris, Paris, France.

Abstract

Editing the fetal γ-globin promoters in hematopoietic stem cells from sickle cell disease patients induces therapeutic γ-globin levels.

Funder

European Research Council

Agence Nationale de la Recherche

Genopole

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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