Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing
H Chao, SG Mansfield, RC Bartel, S Hiriyanna… - Nature medicine, 2003 - nature.com
H Chao, SG Mansfield, RC Bartel, S Hiriyanna, LG Mitchell, MA Garcia-Blanco, CE Walsh
Nature medicine, 2003•nature.comConventional 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 …
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 …
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.
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