RNA repair restores hemoglobin expression in IVS2-654 thalassemic mice.

Svasti, Saovaros; Suwanmanee, Thipparat; Fucharoen, Suthat; Moulton, Hong M; Nelson, Michelle H; Maeda, Nobuyo; Smithies, Oliver; Kole, Ryszard · Proc Natl Acad Sci U S A · 2009

basic_science · Level V

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Abstract

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.

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