|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|
|Date Published||2003 Aug|
|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|
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.
|Alternate Journal||Nat. Med.|