Antisickling effects of an endogenous human alpha-like globin.
Gene replacement or gene reactivation therapies for sickle-cell disease (SCD) typically target the mutant beta(S)-globin subunits of hemoglobin-S (alpha(2)beta(S)(2)) for substitution by nonpathological beta-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 alpha-globin subunits for zeta-globin, an endogenous, developmentally silenced, non-beta-like globin.
He
Zhenning
Z
Department of Medicine (Hematology/Oncology), University of Pennsylvania School of Medicine and The Children's Hospital of Philadelphia, Pennsylvania 19104, USA.
Russell
J Eric
JE
D000818:Animals; D000986:Antisickling Agents / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D005914:Globins / Q000502:physiology / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic
D000986:Antisickling Agents; D005914:Globins