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Protocol
Open Access
  • © Olivier Negre
  • , et al.
  • 2022

Gene Therapy of the β-Hemoglobinopathies by Lentiviral Transfer of the βA(T87Q)-Globin Gene

  • Olivier Negre 1
  • Anne-Virginie Eggimann 1
  • Yves Beuzard 2
  • Jean-Antoine Ribeil 3
  • Philippe Bourget 3
  • Suparerk Borwornpinyo 4
  • Suradej Hongeng 4
  • Salima Hacein-Bey 5
  • Marina Cavazzana 3
  • Philippe Leboulch 2
  • Emmanuel Payen 2
  • 1 - bluebird bio - Cambridge Massachusetts
  • 2 - CEA - Institute of Emerging Disease and Innovative Therapies - Fontenay aux Roses France
  • 3 - Necker Hospital - Assistance Publique-Hôpitaux de Paris - Paris France
  • 4 - Mahidol University - Bangkok - Thailand
  • 5 - Immunology Laboratory - Groupe Hospitalier Universitaire Paris-Sud - Assistance Publique–Hôpitaux de Paris - Paris France

Abstract

β-globin gene disorders are the most prevalent inherited diseases worldwide and result from abnormal β-globin synthesis or structure. Novel therapeutic approaches are being developed in an effort to move beyond palliative management. Gene therapy, by ex vivo lentiviral transfer of a therapeutic β-globin gene derivative (βAT87Q-globin) to hematopoietic stem cells, driven by cis-regulatory elements that confer high, erythroid-specific expression, has been evaluated in human clinical trials over the past 8 years. βAT87Q-globin is used both as a strong inhibitor of HbS polymerization and as a biomarker. While long-term studies are underway in multiple centers in Europe and in the United States, proof-of-principle of efficacy and safety has already been obtained in multiple patients with β-thalassemia and sickle cell disease.