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Dystrophin expression in host muscle following transplantation of muscle precursor cells modified with the phiC31 integrase.
Gene Ther. 2007 Mar; 14(6):514-22.GT

Abstract

Duchenne muscular dystrophy (DMD) is the most severe muscular dystrophy. It is caused by the absence of dystrophin in muscle fibers. The autologous transplantation of genetically corrected muscle precursor cells (MPCs) is a possible cure for DMD. A non-viral method of genetic modification was tested in this study. The co-transfection (nucleofection) of a phiC31 integrase and a transgene expressing plasmid in MPCs led to an increased stable expression in vitro. The stable expression of a small transgene (eGFP) in muscle fibers was initially demonstrated following the transplantation of the genetically modified cells. The stable expression of a truncated version of dystrophin as well as the full-length dystrophin fused with eGFP was then demonstrated in MPCs obtained from an mdx mice. The transplantation of these cells led not only to the expression of these fusion proteins in muscle fibers but also to the reconstitution of the dystrophin complex. Human MPCs were also genetically modified with a plasmid coding for the full-length human dystrophin gene fused with eGFP and transplanted in severe combined immuno deficient mice leading to the expression of eGFP dystrophin in muscle fibers. This work indicates that cell transplantation after correction of MPCs with phiC31 integrase is a possible approach to treat DMD.

Authors+Show Affiliations

Unité de Recherche en Génétique Humaine, Centre de recherche du CHUL, CHUQ, Faculté de Médecine, Université Laval, Sainte-Foy, Québec, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17167499

Citation

Quenneville, S P., et al. "Dystrophin Expression in Host Muscle Following Transplantation of Muscle Precursor Cells Modified With the phiC31 Integrase." Gene Therapy, vol. 14, no. 6, 2007, pp. 514-22.
Quenneville SP, Chapdelaine P, Rousseau J, et al. Dystrophin expression in host muscle following transplantation of muscle precursor cells modified with the phiC31 integrase. Gene Ther. 2007;14(6):514-22.
Quenneville, S. P., Chapdelaine, P., Rousseau, J., & Tremblay, J. P. (2007). Dystrophin expression in host muscle following transplantation of muscle precursor cells modified with the phiC31 integrase. Gene Therapy, 14(6), 514-22.
Quenneville SP, et al. Dystrophin Expression in Host Muscle Following Transplantation of Muscle Precursor Cells Modified With the phiC31 Integrase. Gene Ther. 2007;14(6):514-22. PubMed PMID: 17167499.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dystrophin expression in host muscle following transplantation of muscle precursor cells modified with the phiC31 integrase. AU - Quenneville,S P, AU - Chapdelaine,P, AU - Rousseau,J, AU - Tremblay,J P, Y1 - 2006/11/30/ PY - 2006/12/15/pubmed PY - 2007/6/30/medline PY - 2006/12/15/entrez SP - 514 EP - 22 JF - Gene therapy JO - Gene Ther. VL - 14 IS - 6 N2 - Duchenne muscular dystrophy (DMD) is the most severe muscular dystrophy. It is caused by the absence of dystrophin in muscle fibers. The autologous transplantation of genetically corrected muscle precursor cells (MPCs) is a possible cure for DMD. A non-viral method of genetic modification was tested in this study. The co-transfection (nucleofection) of a phiC31 integrase and a transgene expressing plasmid in MPCs led to an increased stable expression in vitro. The stable expression of a small transgene (eGFP) in muscle fibers was initially demonstrated following the transplantation of the genetically modified cells. The stable expression of a truncated version of dystrophin as well as the full-length dystrophin fused with eGFP was then demonstrated in MPCs obtained from an mdx mice. The transplantation of these cells led not only to the expression of these fusion proteins in muscle fibers but also to the reconstitution of the dystrophin complex. Human MPCs were also genetically modified with a plasmid coding for the full-length human dystrophin gene fused with eGFP and transplanted in severe combined immuno deficient mice leading to the expression of eGFP dystrophin in muscle fibers. This work indicates that cell transplantation after correction of MPCs with phiC31 integrase is a possible approach to treat DMD. SN - 0969-7128 UR - https://www.unboundmedicine.com/medline/citation/17167499/Dystrophin_expression_in_host_muscle_following_transplantation_of_muscle_precursor_cells_modified_with_the_phiC31_integrase_ L2 - http://dx.doi.org/10.1038/sj.gt.3302887 DB - PRIME DP - Unbound Medicine ER -