title: Ribozyme-mediated repair of sickle beta-globin mRNAs in erythrocyte precursors.
abstract: Sickle cell anemia is the most common heritable hematological disease, yet no curative treatment exists for this disorder. Moreover, the intricacies of globin gene expression have made the development of treatments for hemoglobinopathies based on gene therapy difficult. An alternative genetic approach to sickle cell therapy is based on RNA repair. A trans-splicing group I ribozyme was used to alter mutant beta-globin transcripts in erythrocyte precursors derived from peripheral blood from individuals with sickle cell disease. Sickle beta-globin transcripts were converted into messenger RNAs encoding the anti-sickling protein gamma-globin. These results suggest that RNA repair may become a useful approach in the treatment of genetic disorders.
authors.affiliation: Center for Genetic and Cellular Therapies, Department of Surgery, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: N
authors.initials: N
authors.lastname: Lan
authors.forename: R P
authors.initials: RP
authors.lastname: Howrey
authors.forename: S W
authors.initials: SW
authors.lastname: Lee
authors.forename: C A
authors.initials: CA
authors.lastname: Smith
authors.forename: B A
authors.initials: BA
authors.lastname: Sullenger
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood* / Q000628:therapy; D003001:Cloning, Molecular; D015672:Erythroid Precursor Cells / Q000378:metabolism*; D005091:Exons; D005312:Fetal Blood; D015316:Genetic Therapy; D005914:Globins / Q000235:genetics*; D006801:Humans; D009154:Mutation; D016133:Polymerase Chain Reaction; D012326:RNA Splicing; D016337:RNA, Catalytic / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D014529:Uridine / Q000378:metabolism
chemical_list: D016337:RNA, Catalytic; D012333:RNA, Messenger; D005914:Globins; D014529:Uridine