Modulated human globin gene expression: Role for antisense expression vectors

Several approaches have been explored to prevent polymerization of sickle hemoglobin in erythrocytes. We tested the ability of a mammalian expression vector carrying a β gene antisense cDNA fragment to block β gene expression. The antisense expression vector was stably transfected into HS2γβ stable mouse erythroleukemia cell lines producing human γ and β globin chains. By day 14 there was an average 24% decrease and 12% increase in β and γ globin mRNA levels respectively. We observed a loss of β gene inhibition by day 42. This study suggests that a β globin antisense cDNA expression vector may be an alternative gene therapy strategy to decrease sickle hemoglobin levels in patient with sickle cell disease.