Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing.

Imagen de Mariano Garcia-Blanco
TítuloPhenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing.
Publication TypeJournal Article
Year of Publication2003
AutoresChao, H, Mansfield, GS, Bartel, RC, Hiriyanna, S, Mitchell, LG, García-Blanco, MA, Walsh, CE
JournalNat Med
Volume9
Issue8
Pagination1015-9
Date Published2003 Aug
ISSN1078-8956
Palabras claveAnimals, Blood Coagulation, Cell Line, Disease Models, Animal, Factor VIII, Gene Therapy, Hemophilia A, Humans, Mice, Mice, Knockout, Phenotype, RNA, RNA Splicing, Spliceosomes
Abstract

Conventional gene therapy of hemophilia A relies on the transfer of factor VIII (FVIII; encoded by the F8 gene) cDNA. We carried out spliceosome-mediated RNA trans-splicing (SMaRT) to repair mutant FVIII mRNA. A pre-trans-splicing molecule (PTM) corrected endogenous FVIII mRNA in F8 knockout mice with the hemophilia A phenotype, producing sufficient functional FVIII to correct the hemophilia A phenotype. This is the first description of phenotypic correction of a genetic defect by RNA repair in a knockout animal model. Our results indicate the feasibility of using SMaRT to repair RNA for the treatment of genetic diseases.

DOI10.1038/nm900
Alternate JournalNat. Med.
PubMed ID12847523