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

doi:10.1038/nm900

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 journal › Article

129 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 language	English (US)
Pages (from-to)	1015-1019
Number of pages	5
Journal	Nature Medicine
Volume	9
Issue number	8
DOIs	https://doi.org/10.1038/nm900
State	Published - Aug 1 2003
Externally published	Yes

Fingerprint

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

Cite this

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

@article{e0c1399a336b4c1daf706fc4e7097465,

title = "Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing",

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.",

author = "Hengjun Chao and Mansfield, {S. Gary} and Bartel, {Robert C.} and Suja Hiriyanna and Mitchell, {Lloyd G.} and Garcia-Blanco, {Mariano A.} and Walsh, {Christopher E.}",

year = "2003",

month = aug,

day = "1",

doi = "10.1038/nm900",

language = "English (US)",

volume = "9",

pages = "1015--1019",

journal = "Nature Medicine",

issn = "1078-8956",

publisher = "Nature Publishing Group",

number = "8",

}

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 A.

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 -

Access to Document

10.1038/nm900