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

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

Research output: Contribution to journalArticle

402 Citations (Scopus)

Abstract

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 (α2βs 2)] 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
JournalScience
Volume294
Issue number5550
DOIs
StatePublished - Dec 14 2001
Externally publishedYes

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Sickle Cell Anemia
Genetic Therapy
Transgenic Mice
Globins
Erythrocytes
Abnormal Hemoglobins
Splenomegaly
Cell Lineage
Hematopoietic Stem Cells
Dehydration
Point Mutation
Polymerization
Genes
Hemoglobins
Urine
Gene Expression
Proteins

ASJC Scopus subject areas

  • General

Cite this

Pawliuk, R., Westerman, K. A., Fabry, M. E., Payen, E., Tighe, R., Bouhassira, E. E., ... Leboulch, P. (2001). Correction of sickle cell disease in transgenic mouse models by gene therapy. Science, 294(5550), 2368-2371. https://doi.org/10.1126/science.1065806

Correction of sickle cell disease in transgenic mouse models by gene therapy. / Pawliuk, R.; Westerman, K. A.; Fabry, M. E.; Payen, E.; Tighe, R.; Bouhassira, Eric E.; Acharya, S. A.; Ellis, J.; London, I. M.; Eaves, C. J.; Humphries, R. K.; Beuzard, Y.; Nagel, R. L.; Leboulch, P.

In: Science, Vol. 294, No. 5550, 14.12.2001, p. 2368-2371.

Research output: Contribution to journalArticle

Pawliuk, R, Westerman, KA, Fabry, ME, Payen, E, Tighe, R, Bouhassira, EE, Acharya, SA, Ellis, J, London, IM, Eaves, CJ, Humphries, RK, Beuzard, Y, Nagel, RL & Leboulch, P 2001, 'Correction of sickle cell disease in transgenic mouse models by gene therapy', Science, vol. 294, no. 5550, pp. 2368-2371. https://doi.org/10.1126/science.1065806
Pawliuk R, Westerman KA, Fabry ME, Payen E, Tighe R, Bouhassira EE et al. Correction of sickle cell disease in transgenic mouse models by gene therapy. Science. 2001 Dec 14;294(5550):2368-2371. https://doi.org/10.1126/science.1065806
Pawliuk, R. ; Westerman, K. A. ; Fabry, M. E. ; Payen, E. ; Tighe, R. ; Bouhassira, Eric E. ; Acharya, S. A. ; Ellis, J. ; London, I. M. ; Eaves, C. J. ; Humphries, R. K. ; Beuzard, Y. ; Nagel, R. L. ; Leboulch, P. / Correction of sickle cell disease in transgenic mouse models by gene therapy. In: Science. 2001 ; Vol. 294, No. 5550. pp. 2368-2371.
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