RNA repair restores hemoglobin expression in IVS2-654 thalassemic mice

• Main Authors: Saovaros Svasti, Thipparat Suwanmanee, Suthat Fucharoen, Hong M. Moulton, Michelle H. Nelson, Nobuyo Maeda, Oliver Smithies, Ryszard Kole
• Other Authors: The University of North Carolina at Chapel Hill
• Format: Article
• Published: 2018
• Subjects: Multidisciplinary
• Online Access: https://repository.li.mahidol.ac.th/handle/123456789/28397
• Institution: Mahidol University

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. © 2009 by The National Academy of Sciences of the USA.