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Autologous transplantation of muscle precursor cells modified with a lentivirus for muscular dystrophy: human cells and primate models.
Mol Ther. 2007 Feb; 15(2):431-8.MT

Abstract

Duchenne muscular dystrophy (DMD) is characterized by the absence of dystrophin. We tested the ability of lentiviral vectors to deliver a transgene into myogenic cells before their transplantation. Enhanced green fluorescent protein (eGFP) transgene was efficiently transferred into cells and eGFP-positive fibers were generated following transplantation. An eGFP-micro-dystrophin transgene under the control of a cytomegalovirus promoter was then transferred with the same viral vector but caused some toxicity to the mono-nucleated cells. We then used instead a muscle creatine kinase promoter. Dystrophin expression was observed in the muscle fibers after the transplantation of such genetically modified cells into mdx and severe combined immunodeficient mice. Micro-dystrophin expression was also observed in monkey muscles a month after allogenic or autologous transplantation of genetically modified myoblasts. Therapeutic exon skipping was induced by infecting myoblasts of a DMD patient, deleted for dystrophin exons 49 and 50, with a lentivirus expressing a U7 small nuclear RNA containing antisense sequences against exon 51. The modification led to correct exon skipping and to the expression of a quasi-dystrophin in vitro and in vivo. These results demonstrate the feasibility of lentiviral-based ex vivo gene therapy for 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 availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17235323

Citation

Quenneville, Simon P., et al. "Autologous Transplantation of Muscle Precursor Cells Modified With a Lentivirus for Muscular Dystrophy: Human Cells and Primate Models." Molecular Therapy : the Journal of the American Society of Gene Therapy, vol. 15, no. 2, 2007, pp. 431-8.
Quenneville SP, Chapdelaine P, Skuk D, et al. Autologous transplantation of muscle precursor cells modified with a lentivirus for muscular dystrophy: human cells and primate models. Mol Ther. 2007;15(2):431-8.
Quenneville, S. P., Chapdelaine, P., Skuk, D., Paradis, M., Goulet, M., Rousseau, J., Xiao, X., Garcia, L., & Tremblay, J. P. (2007). Autologous transplantation of muscle precursor cells modified with a lentivirus for muscular dystrophy: human cells and primate models. Molecular Therapy : the Journal of the American Society of Gene Therapy, 15(2), 431-8.
Quenneville SP, et al. Autologous Transplantation of Muscle Precursor Cells Modified With a Lentivirus for Muscular Dystrophy: Human Cells and Primate Models. Mol Ther. 2007;15(2):431-8. PubMed PMID: 17235323.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Autologous transplantation of muscle precursor cells modified with a lentivirus for muscular dystrophy: human cells and primate models. AU - Quenneville,Simon P, AU - Chapdelaine,Pierre, AU - Skuk,Daniel, AU - Paradis,Matin, AU - Goulet,Marlyne, AU - Rousseau,Joël, AU - Xiao,Xiao, AU - Garcia,Luis, AU - Tremblay,Jacques P, PY - 2007/1/20/pubmed PY - 2007/6/27/medline PY - 2007/1/20/entrez SP - 431 EP - 8 JF - Molecular therapy : the journal of the American Society of Gene Therapy JO - Mol. Ther. VL - 15 IS - 2 N2 - Duchenne muscular dystrophy (DMD) is characterized by the absence of dystrophin. We tested the ability of lentiviral vectors to deliver a transgene into myogenic cells before their transplantation. Enhanced green fluorescent protein (eGFP) transgene was efficiently transferred into cells and eGFP-positive fibers were generated following transplantation. An eGFP-micro-dystrophin transgene under the control of a cytomegalovirus promoter was then transferred with the same viral vector but caused some toxicity to the mono-nucleated cells. We then used instead a muscle creatine kinase promoter. Dystrophin expression was observed in the muscle fibers after the transplantation of such genetically modified cells into mdx and severe combined immunodeficient mice. Micro-dystrophin expression was also observed in monkey muscles a month after allogenic or autologous transplantation of genetically modified myoblasts. Therapeutic exon skipping was induced by infecting myoblasts of a DMD patient, deleted for dystrophin exons 49 and 50, with a lentivirus expressing a U7 small nuclear RNA containing antisense sequences against exon 51. The modification led to correct exon skipping and to the expression of a quasi-dystrophin in vitro and in vivo. These results demonstrate the feasibility of lentiviral-based ex vivo gene therapy for DMD. SN - 1525-0016 UR - https://www.unboundmedicine.com/medline/citation/17235323/Autologous_transplantation_of_muscle_precursor_cells_modified_with_a_lentivirus_for_muscular_dystrophy:_human_cells_and_primate_models_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1525-0016(16)31298-9 DB - PRIME DP - Unbound Medicine ER -