Correction of sickle cell disease in transgenic mouse models by gene therapy

R. Pawliuk, K. A. Westerman, M. E. Fabry, E. Payen, R. Tighe, E. E. Bouhassira, S. A. Acharya, J. Ellis, I. M. London, C. J. Eaves, R. K. Humphries, Y. Beuzard, R. L. Nagel, P. Leboulch

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Sickle cell disease (SCD) is caused by a single point mutation in the human βA globin gene that results in the formation of an abnormal hemoglobin [HbS (α2βs2)] We designed a ΒA globin gene variant that prevents HbS polymerization and introduced it into a lentiviral vector we optimized for transfer to hematopoietic stem cells and gene expression in the adult red blood cell lineage. Long-term expression (up to 10 months) was achieved, without preselection, in all transplanted mice with erythroid-specific accumulation of the antisickling protein in up to 52% of total hemoglobin and 99% of circulating red blood cells. In two mouse SCD models, Berkeley and SAD, inhibition of red blood cell dehydration and sickling was achieved with correction of hematological parameters, splenomegaly, and prevention of the characteristic urine concentration defect.

Original languageEnglish (US)
Pages (from-to)2368-2371
Number of pages4
Issue number5550
StatePublished - Dec 14 2001

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