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

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Chao, H; Mansfield, SG; Bartel, RC; Hiriyanna, S; Mitchell, LG; Garcia-Blanco, MA; Walsh, CE

Published Date

  • August 2003

Published In

Volume / Issue

  • 9 / 8

Start / End Page

  • 1015 - 1019

PubMed ID

  • 12847523

International Standard Serial Number (ISSN)

  • 1078-8956

Digital Object Identifier (DOI)

  • 10.1038/nm900


  • eng

Conference Location

  • United States