Emerging Genetic Therapy for Sickle Cell Disease.
Annu Rev Med
; 70: 257-271, 2019 01 27.
Article
en En
| MEDLINE
| ID: mdl-30355263
ABSTRACT
The genetic basis of sickle cell disease (SCD) was elucidated >60 years ago, yet current therapy does not rely on this knowledge. Recent advances raise prospects for improved, and perhaps curative, treatment. First, transcription factors, BCL11A and LRF/ZBTB7A, that mediate silencing of the ß-like fetal (γ-) globin gene after birth have been identified and demonstrated to act at the γ-globin promoters, precisely at recognition sequences disrupted in rare individuals with hereditary persistence of fetal hemoglobin. Second, transformative advances in gene editing and progress in lentiviral gene therapy provide diverse opportunities for genetic strategies to cure SCD. Approaches include hematopoietic gene therapy by globin gene addition, gene editing to correct the SCD mutation, and genetic manipulations to enhance fetal hemoglobin production, a potent modifier of the clinical phenotype. Clinical trials may soon identify efficacious and safe genetic approaches to the ultimate goal of cure for SCD.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Represoras
/
Terapia Genética
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Predisposición Genética a la Enfermedad
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Anemia de Células Falciformes
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Female
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Humans
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Male
Idioma:
En
Revista:
Annu Rev Med
Año:
2019
Tipo del documento:
Article