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RNA repair restores hemoglobin expression in IVS2-654 thalassemic mice.
|Title||RNA repair restores hemoglobin expression in IVS2-654 thalassemic mice.|
|Publication Type||Journal Article|
|Year of Publication||2009|
|Authors||Svasti S, Suwanmanee T, Fucharoen S, Moulton HM, Nelson MH, Maeda N, Smithies O, Kole R|
|Journal||Proceedings of the National Academy of Sciences of the United States of America|
|Date Published||2009 Jan 27|
|Keywords||Animals, beta-Globins, Cell Shape, Erythrocytes, Hemoglobins, Humans, Injections, Intravenous, Interleukin-12, Mice, Mutation, Oligonucleotides, RNA Precursors, RNA Splicing, Thalassemia|
Repair of beta-globin pre-mRNA rendered defective by a thalassemia-causing splicing mutation, IVS2-654, in intron 2 of the human beta-globin gene was accomplished in vivo in a mouse model of IVS2-654 thalassemia. This was effected by a systemically delivered splice-switching oligonucleotide (SSO), a morpholino oligomer conjugated to an arginine-rich peptide. The SSO blocked the aberrant splice site in the targeted pre-mRNA and forced the splicing machinery to reselect existing correct splice sites. Repaired beta-globin mRNA restored significant amounts of hemoglobin in the peripheral blood of the IVS2-654 mouse, improving the number and quality of erythroid cells.
|Alternate Journal||Proc. Natl. Acad. Sci. U.S.A.|