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

Hengjun Chao, S. Gary Mansfield, Robert C. Bartel, Suja Hiriyanna, Lloyd G. Mitchell, Mariano A. Garcia-Blanco, Christopher E. Walsh

Research output: Contribution to journalArticlepeer-review

145 Scopus citations


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 languageEnglish (US)
Pages (from-to)1015-1019
Number of pages5
JournalNature Medicine
Issue number8
StatePublished - Aug 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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