• DOI:10.1126/SCIENCE.1065806
• Corpus ID: 25607771

Correction of Sickle Cell Disease in Transgenic Mouse Models by Gene Therapy

@article{Pawliuk2001CorrectionOS,
  title={Correction of Sickle Cell Disease in Transgenic Mouse Models by Gene Therapy},
  author={Robert Pawliuk and Karen A. Westerman and Mary E. Fabry and Emmanuel Payen and Robert Tighe and Eric E. Bouhassira and Seetharama A. Acharya and James Ellis and Irving M. London and Connie J. Eaves and R. Keith Humphries and Yves Beuzard and Ronald L. Nagel and Philippe Leboulch},
  journal={Science},
  year={2001},
  volume={294},
  pages={2368 - 2371}
}

• R. Pawliuk, K. Westerman, +11 authors P. Leboulch
• Published 14 December 2001
• Biology, Medicine
• Science

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.