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 Garcia-Blanco, Christopher E. Walsh

Research output: Contribution to journalArticle

128 Citations (Scopus)

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

Fingerprint

Trans-Splicing
Spliceosomes
Hemophilia A
RNA
Phenotype
Repair
Transfer Factor
Messenger RNA
Inborn Genetic Diseases
Factor VIII
Knockout Mice
Gene therapy
Genetic Therapy
Animal Models
Complementary DNA
Animals
Genes
Defects
Molecules
Therapeutics

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Chao, H., Mansfield, S. G., Bartel, R. C., Hiriyanna, S., Mitchell, L. G., Garcia-Blanco, M., & 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

Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing. / Chao, Hengjun; Mansfield, S. Gary; Bartel, Robert C.; Hiriyanna, Suja; Mitchell, Lloyd G.; Garcia-Blanco, Mariano; Walsh, Christopher E.

In: Nature Medicine, Vol. 9, No. 8, 01.08.2003, p. 1015-1019.

Research output: Contribution to journalArticle

Chao, H, Mansfield, SG, Bartel, RC, Hiriyanna, S, Mitchell, LG, Garcia-Blanco, M & Walsh, CE 2003, 'Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing', Nature Medicine, vol. 9, no. 8, pp. 1015-1019. https://doi.org/10.1038/nm900
Chao, Hengjun ; Mansfield, S. Gary ; Bartel, Robert C. ; Hiriyanna, Suja ; Mitchell, Lloyd G. ; Garcia-Blanco, Mariano ; Walsh, Christopher E. / Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing. In: Nature Medicine. 2003 ; Vol. 9, No. 8. pp. 1015-1019.
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