Saovaros SvastiThipparat SuwanmaneeSuthat FucharoenHong M. MoultonMichelle H. NelsonNobuyo MaedaOliver SmithiesRyszard KoleThe University of North Carolina at Chapel HillThe Institute of Science and Technology for Research and Development, Mahidol UniversityAVI BioPharma Incorporated2018-09-132018-09-132009-01-27Proceedings of the National Academy of Sciences of the United States of America. Vol.106, No.4 (2009), 1205-121010916490002784242-s2.0-59049089272https://repository.li.mahidol.ac.th/handle/20.500.14594/28397Repair 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.Mahidol UniversityMultidisciplinaryArticleSCOPUS10.1073/pnas.0812436106