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Antisickling effects of an endogenous human α-like globin

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Abstract

Gene replacement or gene reactivation therapies for sickle-cell disease (SCD) typically target the mutant βS-globin subunits of hemoglobin-S (α2βS2) for substitution by nonpathological β-like globins. Here we show, in vitro and in vivo in a transgenic mouse model of SCD, that the adverse properties of hemoglobin-S can be reversed by exchanging its normal α-globin subunits for ζ-globin, an endogenous, developmentally silenced, non-β-like globin.

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Figure 1: Antipolymerization properties of hemoglobin-ζ2βS2.
Figure 2: Comparison of informative cellular, biochemical, hematological and functional characteristics of Sα, Sζ and wild-type (Wt) mice.

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Acknowledgements

This research was supported by National Institutes of Health grants HL61399 and HL67118.

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Authors and Affiliations

  1. Department of Medicine (Hematology/Oncology), University of Pennsylvania School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, 19104, Pennsylvania, USA

    Zhenning He & J Eric Russell

  2. Department of Pediatrics (Hematology), University of Pennsylvania School of Medicine and The Children's Hospital of Philadelphia, Philadelphia, 19104, Pennsylvania, USA

    J Eric Russell

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  1. Zhenning He
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  2. J Eric Russell
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Correspondence to J Eric Russell.

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The authors declare no competing financial interests.

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He, Z., Russell, J. Antisickling effects of an endogenous human α-like globin. Nat Med 10, 365–367 (2004). https://doi.org/10.1038/nm1022

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  • DOI: https://doi.org/10.1038/nm1022

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