Frangoul, H. and Altshuler, D. and Cappellini, M. D. and Chen, Y-S and Domm, J. and Eustace, B. K. and Foell, J. and de la Fuente, J. and Grupp, S. and Handgretinger, R. and Ho, T. W. and Kattamis, A. and Kernytsky, A. and Lekstrom-Himes, J. and Li, A. M. and Locatelli, F. and Mapara, M. Y. and de Montalembert, M. and Rondelli, D. and Sharma, A. and Sheth, S. and Soni, S. and Steinberg, M. H. and Wall, D. and Yen, A. and Corbacioglu, S. (2021) CRISPR-Cas9 Gene Editing for Sickle Cell Disease and beta-Thalassemia. NEW ENGLAND JOURNAL OF MEDICINE, 384 (3). pp. 252-260. ISSN 0028-4793, 1533-4406
Full text not available from this repository. (Request a copy)Abstract
Transfusion-dependent beta-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 gamma-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | FETAL-HEMOGLOBIN; RISK-FACTORS; BCL11A; GENOME; TRANSPLANTATION; THERAPY; ASSOCIATION; MORBIDITY; ENHANCER; BLOOD; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Kinder- und Jugendmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Sep 2022 10:12 |
| Last Modified: | 16 Sep 2022 10:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/47536 |
Actions (login required)
 |
View Item |
