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Nat Med. 2003 Aug;9(8):1015-9. Epub 2003 Jul 6.

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

Author information

1
Department of Medicine, Mt. Sinai School of Medicine, New York, New York 10029, USA.

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.

PMID:
12847523
DOI:
10.1038/nm900
[Indexed for MEDLINE]

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