CRISPR-Cas9 Gene Editing for Sickle Cell Disease and ß-Thalassemia.
N Engl J Med
; 384(3): 252-260, 2021 01 21.
Article
en En
| MEDLINE
| ID: mdl-33283989
ABSTRACT
Transfusion-dependent ß-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. (Funded by CRISPR Therapeutics and Vertex Pharmaceuticals; ClinicalTrials.gov numbers, NCT03655678 for CLIMB THAL-111 and NCT03745287 for CLIMB SCD-121.).
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
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Hemoglobina Fetal
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Terapia Genética
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Talasemia beta
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Sistemas CRISPR-Cas
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Edición Génica
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Anemia de Células Falciformes
Límite:
Adult
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Female
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Humans
Idioma:
En
Revista:
N Engl J Med
Año:
2021
Tipo del documento:
Article