Induction of fetal hemoglobin synthesis by CRISPR/Cas9-mediated editing of the human β-globin locus

Author:

Antoniani Chiara12,Meneghini Vasco12ORCID,Lattanzi Annalisa3ORCID,Felix Tristan12ORCID,Romano Oriana124ORCID,Magrin Elisa56ORCID,Weber Leslie25,Pavani Giulia3ORCID,El Hoss Sara7,Kurita Ryo8,Nakamura Yukio8,Cradick Thomas J.9ORCID,Lundberg Ante S.9,Porteus Matthew10ORCID,Amendola Mario3ORCID,El Nemer Wassim7ORCID,Cavazzana Marina25611ORCID,Mavilio Fulvio24ORCID,Miccio Annarita123ORCID

Affiliation:

1. Laboratory of Chromatin and Gene Regulation during Development, Imagine Institute, INSERM Unité Mixte de Recherche (UMR)1163, Paris, France;

2. Paris Descartes, Sorbonne Paris Cité University, Imagine Institute, Paris, France;

3. Genethon, INSERM UMR951, Evry, France;

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

5. Laboratory of Human Lymphohematopoiesis, INSERM UMR1163, Paris, France;

6. Biotherapy Department, Necker Children’s Hospital, Public Assistance Hospitals of Paris, Paris, France;

7. Sorbonne Paris Cité University, Paris Diderot University, INSERM, Institut National de la Transfusion Sanguine, Unité Biologie Intégrée du Globule Rouge, Laboratoire d’Excellence GR-Ex, Paris, France;

8. RIKEN Tsukuba Branch, Ibaraki, Japan;

9. CRISPR Therapeutics, Cambridge, MA;

10. Department of Pediatrics, Stanford University, Stanford, CA; and

11. Biotherapy Clinical Investigation Center, Groupe Hospitalier Universitaire Ouest, Public Assistance Hospitals of Paris, Paris, France

Abstract

Key Points CRISPR/Cas9-mediated disruption of the β-globin locus architecture reactivates fetal γ-globin expression in adult erythroblasts. Fetal γ-globin reactivation and sickle β-globin downregulation leads to the amelioration of the SCD cell phenotype.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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