RNA repair restores hemoglobin expression in IVS2–654 thalassemic mice
S Svasti, T Suwanmanee… - Proceedings of the …, 2009 - National Acad Sciences
S Svasti, T Suwanmanee, S Fucharoen, HM Moulton, MH Nelson, N Maeda, O Smithies…
Proceedings of the National Academy of Sciences, 2009•National Acad SciencesRepair of β-globin pre-mRNA rendered defective by a thalassemia-causing splicing
mutation, IVS2–654, in intron 2 of the human β-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 β-globin mRNA …
mutation, IVS2–654, in intron 2 of the human β-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 β-globin mRNA …
Repair of β-globin pre-mRNA rendered defective by a thalassemia-causing splicing mutation, IVS2–654, in intron 2 of the human β-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 β-globin mRNA restored significant amounts of hemoglobin in the peripheral blood of the IVS2–654 mouse, improving the number and quality of erythroid cells.
National Acad Sciences