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siRNA-mediated reduction of -globin results in phenotypic improvements in β-thalassemic cells

Cell and Gene Therapy Research Group, The Murdoch Children’s Research Institute, The University of Melbourne, Royal Children’s Hospital, Parkville, Melbourne, Australia

Correspondence: Jim Vadolas, Cell and Gene Therapy Research Group, The Murdoch Childrens Research Institute, The University of Melbourne, Royal Children’s Hospital, Flemington Road, Parkville 3052, Melbourne, Australia. E-mail:jim.vadolas{at}mcri.edu.au

β-thalassemia is an inherited hemoglobinopathy caused by defective synthesis of the β-globin chain of hemoglobin, leading to imbalanced globin chain synthesis. Excess -globin precipitates in erythroid progenitor cells resulting in cell death, ineffective erythropoiesis and severe anemia. Decreased -globin synthesis leads to milder symptoms, exemplified in individuals who co-inherit - and β-thalassemia. In this study, we investigated the feasibility of utilizing short-interfering RNA (siRNA) to mediate reductions in -globin expression. A number of siRNA sequences targeting murine -globin were tested in hemoglobinized murine erythroleukemic cells. One highly effective siRNA sequence (si- 4) was identified and reduced -globin by approximately 65% at both the RNA and the protein level. Electroporation of si- 4 into murine thalassemic primary erythroid cultures restored :β-globin ratios to balanced wild-type levels and resulted in detectable phenotypic correction. These results indicate that siRNA-mediated reduction of -globin has potential therapeutic applications in the treatment of β-thalassemia.

Key words: siRNA-mediated reduction, -globin, phenotypic, β-thalassemic cells.

This article has been cited by other articles:

				H. P. J. Voon and J. Vadolas Controlling {alpha}-globin: a review of {alpha}-globin expression and its impact on {beta}-thalassemia Haematologica, December 1, 2008; 93(12): 1868 - 1876. [Abstract] [Full Text] [PDF]