RESUMEN

Sickle cell anemia affects millions of people worldwide and is an emerging global health burden. As part of a large NIH-funded NextGen Consortium, we generated a diverse, comprehensive, and fully characterized library of sickle-cell-disease-specific induced pluripotent stem cells (iPSCs) from patients of different ethnicities, ß-globin gene (HBB) haplotypes, and fetal hemoglobin (HbF) levels. iPSCs stand to revolutionize the way we study human development, model disease, and perhaps eventually, treat patients. Here, we describe this unique resource for the study of sickle cell disease, including novel haplotype-specific polymorphisms that affect disease severity, as well as for the development of patient-specific therapeutics for this phenotypically diverse disorder. As a complement to this library, and as proof of principle for future cell- and gene-based therapies, we also designed and employed CRISPR/Cas gene editing tools to correct the sickle hemoglobin (HbS) mutation.

Asunto(s)

Anemia de Células Falciformes/genética , Anemia de Células Falciformes/terapia , Sistemas CRISPR-Cas , Terapia Genética , Hemoglobina Falciforme/genética , Células Madre Pluripotentes Inducidas/metabolismo , Globinas beta/genética , Adolescente , Adulto , Anemia de Células Falciformes/sangre , Anemia de Células Falciformes/etnología , Secuencia de Bases , Línea Celular , Células Cultivadas , Niño , Preescolar , Células Eritroides/citología , Células Eritroides/metabolismo , Femenino , Hemoglobina Fetal/análisis , Terapia Genética/métodos , Haplotipos , Humanos , Células Madre Pluripotentes Inducidas/citología , Masculino , Persona de Mediana Edad , Mutación Puntual , Polimorfismo Genético , Transcriptoma , Adulto Joven