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Correction of glycogenosis type 2 by muscle-specific lentiviral vector.
In Vitro Cell Dev Biol Anim. 2008 Nov-Dec; 44(10):397-406.VC

Abstract

Glycogen storage disease type II (GSDII) or Pompe disease is an inherited disease of glycogen metabolism caused by a lack of functional lysosomal acid alpha-glucosidase (GAA). Affected individuals store glycogen in lysosomes resulting in fatal hypertrophic cardiomyopathy and respiratory failure in the most severe form. We investigated for the first time the use of lentiviral vectors to correct the GSDII phenotype in human and murine GAA-deficient cells. Fibroblasts from infantile and adult GSDII patients were efficiently transduced by a GAA-expressing lentiviral vector placed under the control of the strong MND promoter, leading to a complete restoration of enzymatic activity. We also developed a muscle-specific lentiviral vector based on the synthetic C5-12 promoter and tested it on deficient myogenic satellite cells derived from a GSDII mouse model. GAA was expressed as a correctly processed protein allowing a complete enzymatic and metabolic correction in myoblasts and differentiated myotubes, as well as a significant mannose-6-phosphate (M6P)-dependent secretion reuptake by naive cells. Transduced cells showed lysosomal glycogen clearance, as demonstrated by electron microscopy. These results form the basis for a therapeutic approach of GSDII using lentiviral vector-mediated gene transfer into muscle stem cells.

Authors+Show Affiliations

Institut Cochin, Université Paris Descartes, CNRS UMR 8104, INSERM U567, Paris, France. Emmanuel.Richard@u-bordeaux2.frNo 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

18810562

Citation

Richard, Emmanuel, et al. "Correction of Glycogenosis Type 2 By Muscle-specific Lentiviral Vector." In Vitro Cellular & Developmental Biology. Animal, vol. 44, no. 10, 2008, pp. 397-406.
Richard E, Douillard-Guilloux G, Batista L, et al. Correction of glycogenosis type 2 by muscle-specific lentiviral vector. In Vitro Cell Dev Biol Anim. 2008;44(10):397-406.
Richard, E., Douillard-Guilloux, G., Batista, L., & Caillaud, C. (2008). Correction of glycogenosis type 2 by muscle-specific lentiviral vector. In Vitro Cellular & Developmental Biology. Animal, 44(10), 397-406. https://doi.org/10.1007/s11626-008-9138-5
Richard E, et al. Correction of Glycogenosis Type 2 By Muscle-specific Lentiviral Vector. In Vitro Cell Dev Biol Anim. 2008 Nov-Dec;44(10):397-406. PubMed PMID: 18810562.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Correction of glycogenosis type 2 by muscle-specific lentiviral vector. AU - Richard,Emmanuel, AU - Douillard-Guilloux,Gaëlle, AU - Batista,Lionel, AU - Caillaud,Catherine, Y1 - 2008/09/23/ PY - 2008/05/29/received PY - 2008/07/18/accepted PY - 2008/9/24/pubmed PY - 2009/5/19/medline PY - 2008/9/24/entrez SP - 397 EP - 406 JF - In vitro cellular & developmental biology. Animal JO - In Vitro Cell Dev Biol Anim VL - 44 IS - 10 N2 - Glycogen storage disease type II (GSDII) or Pompe disease is an inherited disease of glycogen metabolism caused by a lack of functional lysosomal acid alpha-glucosidase (GAA). Affected individuals store glycogen in lysosomes resulting in fatal hypertrophic cardiomyopathy and respiratory failure in the most severe form. We investigated for the first time the use of lentiviral vectors to correct the GSDII phenotype in human and murine GAA-deficient cells. Fibroblasts from infantile and adult GSDII patients were efficiently transduced by a GAA-expressing lentiviral vector placed under the control of the strong MND promoter, leading to a complete restoration of enzymatic activity. We also developed a muscle-specific lentiviral vector based on the synthetic C5-12 promoter and tested it on deficient myogenic satellite cells derived from a GSDII mouse model. GAA was expressed as a correctly processed protein allowing a complete enzymatic and metabolic correction in myoblasts and differentiated myotubes, as well as a significant mannose-6-phosphate (M6P)-dependent secretion reuptake by naive cells. Transduced cells showed lysosomal glycogen clearance, as demonstrated by electron microscopy. These results form the basis for a therapeutic approach of GSDII using lentiviral vector-mediated gene transfer into muscle stem cells. SN - 1543-706X UR - https://www.unboundmedicine.com/medline/citation/18810562/Correction_of_glycogenosis_type_2_by_muscle_specific_lentiviral_vector_ L2 - https://dx.doi.org/10.1007/s11626-008-9138-5 DB - PRIME DP - Unbound Medicine ER -