摘要
Transfusion-dependent β-thalassemia(TDT)and sickle cell disease(SCD)are severe monogenic diseases with severe and potentially life-threatening manifestations.BCL11A is a transcription factor that represses γ-globin expression and fetal hemoglobin in erythroid cells.We performed electroporation of CD34+hematopoietic stem and progenitor cells obtained from healthy donors,with CRISPR-Cas9 targeting the BCL11A erythroid-specific enhancer.Approximately 80% of the alleles at this locus were modified,with no evidence of off-target editing.After undergoing myeloablation,two patients-one with TDT and the other with SCD-received autologous CD34+cells edited with CRISPR-Cas9 targeting the same BCL11A enhancer.More 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.
出处
《四川生理科学杂志》
2020年第4期506-506,共1页
Sichuan Journal of Physiological Sciences
