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={R. Pawliuk and K. Westerman and M. Fabry and E. Payen and R. Tighe and E. Bouhassira and S. Acharya and J. Ellis and I. London and C. Eaves and R. Humphries and Y. Beuzard and R. Nagel and P. Leboulch},
  journal={Science},
  year={2001},
  volume={294},
  pages={2368 - 2371}
}
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… Expand
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The data in this paper demonstrate that sickle cell disease can be corrected without the risk of insertional mutagenesis and provide a foundation for similar studies in human ES cells derived from sickle Cell patients. Expand
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References

The molecular basis of blood diseases
TLDR
The molecular and Biological properties of the Human Immunodeficiency Virus Viral Pathogenesis of Hematological Disorders B19 Parvoviruses HTLVs Herpesviruses and the Gene Therapy of Hemopoietic Diseases are studied. Expand