Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing.
Enviado por Mariano Garcia-Blanco el
PDF version| Título | Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing. |
| Publication Type | Journal Article |
| Year of Publication | 2003 |
| Autores | Chao, H, Mansfield, GS, Bartel, RC, Hiriyanna, S, Mitchell, LG, García-Blanco, MA, Walsh, CE |
| Journal | Nat Med |
| Volume | 9 |
| Issue | 8 |
| Pagination | 1015-9 |
| Date Published | 2003 Aug |
| ISSN | 1078-8956 |
| Palabras clave | Animals, 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. |
| DOI | 10.1038/nm900 |
| Alternate Journal | Nat. Med. |
| PubMed ID | 12847523 |
