title: RNA repair restores hemoglobin expression in IVS2-654 thalassemic mice.
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.
authors.affiliation: Department of Pharmacology, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Saovaros
authors.initials: S
authors.lastname: Svasti
authors.forename: Thipparat
authors.initials: T
authors.lastname: Suwanmanee
authors.forename: Suthat
authors.initials: S
authors.lastname: Fucharoen
authors.forename: Hong M
authors.initials: HM
authors.lastname: Moulton
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Nelson
authors.forename: Nobuyo
authors.initials: N
authors.lastname: Maeda
authors.forename: Oliver
authors.initials: O
authors.lastname: Smithies
authors.forename: Ryszard
authors.initials: R
authors.lastname: Kole
mesh_terms: D000818:Animals; D048430:Cell Shape / Q000187:drug effects; D004912:Erythrocytes / Q000187:drug effects / Q000473:pathology; D006454:Hemoglobins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007275:Injections, Intravenous; D018664:Interleukin-12 / Q000097:blood; D051379:Mice; D009154:Mutation / Q000235:genetics*; D009841:Oligonucleotides / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology; D012322:RNA Precursors / Q000235:genetics* / Q000378:metabolism; D012326:RNA Splicing / Q000187:drug effects / Q000235:genetics; D013789:Thalassemia / Q000097:blood / Q000235:genetics* / Q000628:therapy*; D055544:beta-Globins / Q000235:genetics
chemical_list: D006454:Hemoglobins; D009841:Oligonucleotides; D012322:RNA Precursors; D055544:beta-Globins; D018664:Interleukin-12