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 language | English (US) |
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Pages (from-to) | 1015-1019 |
Number of pages | 5 |
Journal | Nature Medicine |
Volume | 9 |
Issue number | 8 |
DOIs | |
State | Published - Aug 1 2003 |
Externally published | Yes |
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ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing
AU - Chao, Hengjun
AU - Mansfield, S. Gary
AU - Bartel, Robert C.
AU - Hiriyanna, Suja
AU - Mitchell, Lloyd G.
AU - Garcia-Blanco, Mariano
AU - Walsh, Christopher E.
PY - 2003/8/1
Y1 - 2003/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0042388694&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0042388694&partnerID=8YFLogxK
U2 - 10.1038/nm900
DO - 10.1038/nm900
M3 - Article
C2 - 12847523
AN - SCOPUS:0042388694
VL - 9
SP - 1015
EP - 1019
JO - Nature Medicine
JF - Nature Medicine
SN - 1078-8956
IS - 8
ER -