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 M. E. Fabry and Emmanuel Payen and Robert Tighe and Eric E. Bouhassira and Seetharama A. Acharya and James Ellis and Irving M. London and C. 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}
}
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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509 Citations

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Gene replacement therapy for sickle cell disease and other blood disorders.
  • T. Townes
  • Biology, Medicine
  • Hematology. American Society of Hematology. Education Program
  • 2008
TLDR
Proof-of-principle studies provide a foundation for the development of gene replacement therapy for human patients with SCD and other blood disorders. Expand
Correction of sickle cell disease by homologous recombination in embryonic stem cells.
TLDR
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
Gene Therapy in a Patient with Sickle Cell Disease.
  • J. Ribeil
  • Medicine
  • The New England journal of medicine
  • 2017
TLDR
First patient treated with lentiviral vector–mediated addition of an antisickling β-globin gene into autologous hematopoietic stem cells without recurrence of sickle crises and with correction of the biologic hallmarks of the disease is described. Expand
Globin gene transfer for treatment of the β-thalassemias and sickle cell disease
TLDR
Using lentiviral vectors, it is demonstrated that an optimised combination of proximal and distal transcriptional control elements permits lineage-specific, elevated expression of the β-globin gene, resulting in therapeutic hemoglobin production and correction of anemia in β-thalassemic mice. Expand
Correction of Sickle Cell Disease in Adult Mice by Interference with Fetal Hemoglobin Silencing
TLDR
It is demonstrated that inactivation of BCL11A in SCD transgenic mice corrects the hematologic and pathologic defects associated with SCD through high-level pancellular HbF induction. Expand
Gene Therapy in a Patient with Sickle Cell Disease: Brief Report
TLDR
First patient treated with lentiviral vector–mediated addition of an antisickling β‐globin gene into autologous hematopoietic stem cells without recurrence of sickle crises and with correction of the biologic hallmarks of the disease is described. Expand
Gene Therapy in Sickle Cell Disease
Sickle cell disease is a prevalent and severe monogenic disorder resulting from a homozygous missense mutation in the β-globin gene that leads to polymerization of hemoglobin S. Clinical… Expand
Sickle cell gene therapy
TLDR
An optimized lentiviral vector based on HIV-1 was used to transduce murine bone marrow cells with a modified human β-globin gene, βA-T87Q, that inhibits the effect of abnormal sickle cell hemoglobin (HbS) in mice suggesting that long-term correction of SCD could be possible. Expand
A novel human gamma-globin gene vector for genetic correction of sickle cell anemia in a humanized sickle mouse model: critical determinants for successful correction.
TLDR
These studies provide a strong preclinical model for what it would take to genetically correct sickle cell anemia (SCA) and are a foundation for the use of this vector in a human clinical trial. Expand
Correction of Murine Sickle Cell Disease Using γ-Globin Lentiviral Vectors to Mediate High-level Expression of Fetal Hemoglobin.
TLDR
The rationale for a gene therapy approach to SCD by permanently enhancing HbF using a γ-globin lentiviral vector is supported. 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