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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1015-1019 |
| Number of pages | 5 |
| Journal | Nature Medicine |
| Volume | 9 |
| Issue number | 8 |
| DOIs | |
| State | Published - Aug 1 2003 |
| Externally published | Yes |
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
Fingerprint Dive into the research topics of 'Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing'. Together they form a unique fingerprint.
Cite this
Chao, H., Mansfield, S. G., Bartel, R. C., Hiriyanna, S., Mitchell, L. G., Garcia-Blanco, M. A., & Walsh, C. E. (2003). Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing. Nature Medicine, 9(8), 1015-1019. https://doi.org/10.1038/nm900