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

150 Scopus citations

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 languageEnglish
Pages (from-to)1015-1019
Number of pages5
JournalNature Medicine
Volume9
Issue number8
DOIs
StatePublished - 1 Aug 2003

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