Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector.

Hdl Handle:
http://hdl.handle.net/10147/237971
Title:
Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector.
Authors:
Luo, Xiaoyan; Hall, Gentzon; Li, Songtao; Bird, Andrew; Lavin, Peter J; Winn, Michelle P; Kemper, Alex R; Brown, Talmage T; Koeberl, Dwight D
Affiliation:
Department of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.
Citation:
Hepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector. 2011, 19 (11):1961-70 Mol. Ther.
Journal:
Molecular therapy : the journal of the American Society of Gene Therapy
Issue Date:
Nov-2011
URI:
http://hdl.handle.net/10147/237971
DOI:
10.1038/mt.2011.126
PubMed ID:
21730973
Additional Links:
http://www.ncbi.nlm.nih.gov/pubmed?term=Hepatorenal%20Correction%20in%20Murine%20Glycogen%20Storage%20Disease%20Type%20I%20with%20a%20Double-stranded%20Adeno-associated%20Virus%20Vector
Abstract:
Glycogen storage disease type Ia (GSD-Ia) is caused by the deficiency of glucose-6-phosphatase (G6Pase). Long-term complications of GSD-Ia include life-threatening hypoglycemia and proteinuria progressing to renal failure. A double-stranded (ds) adeno-associated virus serotype 2 (AAV2) vector encoding human G6Pase was pseudotyped with four serotypes, AAV2, AAV7, AAV8, and AAV9, and we evaluated efficacy in 12-day-old G6pase (-/-) mice. Hypoglycemia during fasting (plasma glucose <100 mg/dl) was prevented for >6 months by the dsAAV2/7, dsAAV2/8, and dsAAV2/9 vectors. Prolonged fasting for 8 hours revealed normalization of blood glucose following dsAAV2/9 vector administration at the higher dose. The glycogen content of kidney was reduced by >65% with both the dsAAV2/7 and dsAAV2/9 vectors, and renal glycogen content was stably reduced between 7 and 12 months of age for the dsAAV2/9 vector-treated mice. Every vector-treated group had significantly reduced glycogen content in the liver, in comparison with untreated G6pase (-/-) mice. G6Pase was expressed in many renal epithelial cells of with the dsAAV2/9 vector for up to 12 months. Albuminuria and renal fibrosis were reduced by the dsAAV2/9 vector. Hepatorenal correction in G6pase (-/-) mice demonstrates the potential of AAV vectors for the correction of inherited diseases of metabolism.
Item Type:
Article
Language:
en
MeSH:
Animals; Dependovirus; Disease Models, Animal; Female; Gene Expression Regulation; Gene Therapy; Genetic Vectors; Glucose-6-Phosphatase; Glycogen Storage Disease Type I; Humans; Hypoglycemia; Kaplan-Meier Estimate; Kidney; Liver; Male; Mice; Mice, Knockout
ISSN:
1525-0024

Full metadata record

DC FieldValue Language
dc.contributor.authorLuo, Xiaoyanen_GB
dc.contributor.authorHall, Gentzonen_GB
dc.contributor.authorLi, Songtaoen_GB
dc.contributor.authorBird, Andrewen_GB
dc.contributor.authorLavin, Peter Jen_GB
dc.contributor.authorWinn, Michelle Pen_GB
dc.contributor.authorKemper, Alex Ren_GB
dc.contributor.authorBrown, Talmage Ten_GB
dc.contributor.authorKoeberl, Dwight Den_GB
dc.date.accessioned2012-08-09T13:18:45Z-
dc.date.available2012-08-09T13:18:45Z-
dc.date.issued2011-11-
dc.identifier.citationHepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector. 2011, 19 (11):1961-70 Mol. Ther.en_GB
dc.identifier.issn1525-0024-
dc.identifier.pmid21730973-
dc.identifier.doi10.1038/mt.2011.126-
dc.identifier.urihttp://hdl.handle.net/10147/237971-
dc.description.abstractGlycogen storage disease type Ia (GSD-Ia) is caused by the deficiency of glucose-6-phosphatase (G6Pase). Long-term complications of GSD-Ia include life-threatening hypoglycemia and proteinuria progressing to renal failure. A double-stranded (ds) adeno-associated virus serotype 2 (AAV2) vector encoding human G6Pase was pseudotyped with four serotypes, AAV2, AAV7, AAV8, and AAV9, and we evaluated efficacy in 12-day-old G6pase (-/-) mice. Hypoglycemia during fasting (plasma glucose <100 mg/dl) was prevented for >6 months by the dsAAV2/7, dsAAV2/8, and dsAAV2/9 vectors. Prolonged fasting for 8 hours revealed normalization of blood glucose following dsAAV2/9 vector administration at the higher dose. The glycogen content of kidney was reduced by >65% with both the dsAAV2/7 and dsAAV2/9 vectors, and renal glycogen content was stably reduced between 7 and 12 months of age for the dsAAV2/9 vector-treated mice. Every vector-treated group had significantly reduced glycogen content in the liver, in comparison with untreated G6pase (-/-) mice. G6Pase was expressed in many renal epithelial cells of with the dsAAV2/9 vector for up to 12 months. Albuminuria and renal fibrosis were reduced by the dsAAV2/9 vector. Hepatorenal correction in G6pase (-/-) mice demonstrates the potential of AAV vectors for the correction of inherited diseases of metabolism.en_GB
dc.language.isoenen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed?term=Hepatorenal%20Correction%20in%20Murine%20Glycogen%20Storage%20Disease%20Type%20I%20with%20a%20Double-stranded%20Adeno-associated%20Virus%20Vectoren_GB
dc.rightsArchived with thanks to Molecular therapy : the journal of the American Society of Gene Therapyen_GB
dc.subject.meshAnimals-
dc.subject.meshDependovirus-
dc.subject.meshDisease Models, Animal-
dc.subject.meshFemale-
dc.subject.meshGene Expression Regulation-
dc.subject.meshGene Therapy-
dc.subject.meshGenetic Vectors-
dc.subject.meshGlucose-6-Phosphatase-
dc.subject.meshGlycogen Storage Disease Type I-
dc.subject.meshHumans-
dc.subject.meshHypoglycemia-
dc.subject.meshKaplan-Meier Estimate-
dc.subject.meshKidney-
dc.subject.meshLiver-
dc.subject.meshMale-
dc.subject.meshMice-
dc.subject.meshMice, Knockout-
dc.titleHepatorenal correction in murine glycogen storage disease type I with a double-stranded adeno-associated virus vector.en_GB
dc.typeArticleen
dc.contributor.departmentDepartment of Pediatrics, Division of Medical Genetics, Duke University Medical Center, Durham, North Carolina 27710, USA.en_GB
dc.identifier.journalMolecular therapy : the journal of the American Society of Gene Therapyen_GB
dc.description.provinceLeinsteren
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