TitleRNA repair restores hemoglobin expression in IVS2-654 thalassemic mice.
Publication TypeJournal Article
Year of Publication2009
AuthorsSvasti, S, Suwanmanee, T, Fucharoen, S, Moulton, HM, Nelson, MH, Maeda, N, Smithies, O, Kole, R
JournalProceedings of the National Academy of Sciences of the United States of America
Date Published2009 Jan 27

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.