CRISPR-Cas9 Gene Editing for Sickle Cell Disease and β-Thalassemia

作     者：Haydar Frangoul 

作者机构：From the Sarah Cannon Center for Blood Cancer at the Children’s Hospital at TriStar Centennial Nashville (H.F. J.D.) and St. Jude Children’s Research Hospital Memphis (A.S.) — both in Tennessee Vertex Pharmaceuticals (D.A. B.K.E. J.L.-H. A.Y.) and Boston University School of Medicine (M.H.S.) Boston and CRISPR Therapeutics Cambridge (Y.-S.C. T.W.H. A. Kernytsky S. Soni) — both in Massachusetts the University of Milan Milan (M.D.C.) and Ospedale Pediatrico Bambino Gesù Rome Sapienza University of Rome Rome (F.L.) the University of Regensburg Regensburg (J. Foell S.C.) and Children’s University Hospital University of Tübingen Tübingen (R.H.) — both in Germany Imperial College Healthcare NHS Trust St. Mary’s Hospital London (J. de la Fuente) Children’s Hospital of Philadelphia Perelman School of Medicine at the University of Pennsylvania Philadelphia (S.G.) the University of Athens Athens (A. Kattamis) BC Children’s Hospital University of British Columbia Vancouver (A.M.L.) and the Hospital for Sick Children–University of Toronto Toronto (D.W.) — both in Canada Columbia University (M.Y.M.) and the Joan and Sanford I. Weill Medical College of Cornell University (S. Sheth) New York Necker–Enfants Malades Hospital Assistance Publique–Hôpitaux de Paris University of Paris Paris (M.M.) and the University of Illinois at Chicago Chicago (D.R.). 

出 版 物：《四川生理科学杂志》 (Sichuan Journal of Physiological Sciences)

年 卷 期：2020年第42卷第4期

页      面：506-506页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

主　　题：fetal transfusion patients 

摘      要：Transfusion-dependent β-thalassemia(TDT)and sickle cell disease(SCD)are severe monogenic diseases with severe and potentially life-threatening ***11A is a transcription factor that represses γ-globin expression and fetal hemoglobin in erythroid *** performed electroporation of CD34+hematopoietic stem and progenitor cells obtained from healthy donors,with CRISPR-Cas9 targeting the BCL11A erythroid-specific *** 80% of the alleles at this locus were modified,with no evidence of off-target *** undergoing myeloablation,two patients-one with TDT and the other with SCD-received autologous CD34+cells edited with CRISPR-Cas9 targeting the same BCL11A *** than a year later,both patients had high levels of allelic editing in bone marrow and blood,increases in fetal hemoglobin that were distributed pancellularly,transfusion independence,and(in the patient with SCD)elimination of vaso-occlusive episodes.